U.S. GOVERNMENT PRINTING OFFICE

WASHINGTON : 

For sale by the Superintendent of Documents, U.S. Government Printing Office

Internet: bookstore.gpo.gov Phone: toll free (866) 512–1800; DC area (202) 512–1800

Fax: (202) 512–2104 Mail: Stop IDCC, Washington, DC 20402–0001

80–903 PDF 2013

S. HRG. 108–949 

ADVANCES IN ADULT AND NON-EMBRYONIC 

STEM CELL RESEARCH 

HEARING 

BEFORE THE

SUBCOMMITTEE ON SCIENCE, TECHNOLOGY, 

AND SPACE 

OF THE

COMMITTEE ON COMMERCE, 

SCIENCE, AND TRANSPORTATION 

UNITED STATES SENATE 

ONE HUNDRED EIGHTH CONGRESS 

FIRST SESSION 

JUNE 12, 2003 

Printed for the use of the Committee on Commerce, Science, and Transportation 

( 

(II) 

SENATE COMMITTEE ON COMMERCE, SCIENCE, AND TRANSPORTATION 

ONE HUNDRED EIGHTH CONGRESS 

FIRST SESSION 

JOHN MCCAIN, Arizona, Chairman 

TED STEVENS, Alaska 

CONRAD BURNS, Montana 

TRENT LOTT, Mississippi 

KAY BAILEY HUTCHISON, Texas 

OLYMPIA J. SNOWE, Maine 

SAM BROWNBACK, Kansas 

GORDON H. SMITH, Oregon 

PETER G. FITZGERALD, Illinois 

JOHN ENSIGN, Nevada 

GEORGE ALLEN, Virginia 

JOHN E. SUNUNU, New Hampshire 

ERNEST F. HOLLINGS, South Carolina, 

Ranking 

DANIEL K. INOUYE, Hawaii 

JOHN D. ROCKEFELLER IV, West Virginia 

JOHN F. KERRY, Massachusetts 

JOHN B. BREAUX, Louisiana 

BYRON L. DORGAN, North Dakota 

RON WYDEN, Oregon 

BARBARA BOXER, California 

BILL NELSON, Florida 

MARIA CANTWELL, Washington 

FRANK R. LAUTENBERG, New Jersey 

JEANNE BUMPUS, Republican Staff Director and General Counsel 

ROBERT W. CHAMBERLIN, Republican Chief Counsel 

KEVIN D. KAYES, Democratic Staff Director and Chief Counsel 

GREGG ELIAS, Democratic General Counsel 

SUBCOMMITTEE ON SCIENCE, TECHNOLOGY, AND SPACE 

SAM BROWNBACK, Kansas, Chairman 

TED STEVENS, Alaska 

CONRAD BURNS, Montana 

TRENT LOTT, Mississippi 

KAY BAILEY HUTCHISON, Texas 

JOHN ENSIGN, Nevada 

GEORGE ALLEN, Virginia 

JOHN E. SUNUNU, New Hampshire 

JOHN B. BREAUX, Louisiana, Ranking 

JOHN D. ROCKEFELLER IV, West Virginia 

JOHN F. KERRY, Massachusetts 

BYRON L. DORGAN, North Dakota 

RON WYDEN, Oregon 

BILL NELSON, Florida 

FRANK R. LAUTENBERG, New Jersey 

(III) 

C O N T E N T S 

Page 

Hearing held on June 12, 2003 ............................................................................... 1 

Statement of Senator Brownback ........................................................................... 1 

Prepared statement .......................................................................................... 2 

WITNESSES

Barsh, Steven L., Merion Station, Pennsylvania .................................................. 40 

Prepared statement .......................................................................................... 42 

Hess, David C., Professor and Chairman, Department of Neurology, Medical 

College of Georgia ................................................................................................ 3 

Prepared statement .......................................................................................... 6 

Kurtzberg, M.D., Joanne, Director, Pediatric Stem Cell Transplant Program, 

Duke University Medical Center ........................................................................ 11 

Prepared statement .......................................................................................... 15 

McDonald, M.D., Ph.D., John, on behalf of the Coalition for the Advancement 

of Medical Research ............................................................................................. 23 

Prepared statement .......................................................................................... 25 

Peduzzi-Nelson, Ph.D., Jean D., Department of Physiological Optics, University of Alabama at Birmingham .......................................................................... 26 

Prepared statement .......................................................................................... 28 

Penn, Keone, Snellville, Georgia ............................................................................ 47 

Prepared statement .......................................................................................... 48 

Rubinstein, M.D., Pablo, Director of Placental Blood Program, New York 

Blood Center ......................................................................................................... 9 

Prepared statement .......................................................................................... 15 

Sprague, Stephen R., Staten Island, New York .................................................... 44 

Prepared statement .......................................................................................... 45 

APPENDIX

Testimony of the American Academy of Physician Assistants ............................ 55 

(1) 

ADVANCES IN ADULT AND NON-EMBRYONIC 

STEM CELL RESEARCH 

THURSDAY, JUNE 12, 2003, 

U.S. SENATE, SUBCOMMITTEE ON SCIENCE, TECHNOLOGY, AND SPACE, COMMITTEE ON COMMERCE, SCIENCE, AND TRANSPORTATION, Washington, DC. 

The Subcommittee met, pursuant to notice, at 2:46 p.m. in room 

SR–253, Russell Senate Office Building, Hon. Sam Brownback, 

Chairman of the Subcommittee, presiding. 

OPENING STATEMENT OF HON. SAM BROWNBACK, 

U.S. SENATOR FROM KANSAS 

Senator BROWNBACK. The hearing will come to order. I want to 

thank everybody for being here today, particularly the witnesses 

that traveled some distance. We have a couple of really special 

ones—not that all of you aren’t special, but I think you’re going to 

find these just particularly heartening stories of incredible things 

that have taken place. 

Today, we’ll be conducting a hearing on some of the exciting new 

advances being made in the fields of adult and non-embryonic stem 

cell research. As I’m sure many of you know, the field of regenerative medicine offers great hope to those suffering from this disease. 

Much of the research that is providing new hope to those who are 

currently suffering is moving along at a fast pace and is doing so 

without questionable or morally controversial techniques. 

At this hearing, we will examine some of these advances. This 

hearing is not about human cloning or destructive human embryonic stem cell research. Rather, it is about some of the other important scientific discoveries that are being made using noncontroversial techniques that rely on adult or non-embryonic stem cells. And 

these are some processes that only a year-and-a-half ago, we’ll recall, were being called ‘‘junk science.’’ And yet you’re going to hear 

today from people that have been cured. So there’s been amazing 

work, fabulous work, that has really resulted in people’s lives being 

changed. 

In particular today, we will hear from cord-blood stem cell researchers, as well as others, who are working hard in the field of 

regenerative medicine to find the cures to the diseases that plague 

humanity. At this hearing, we will discuss not only some of the research that is being conducted, but also some of the treatments 

that are currently being offered. And we will hear from some of the 

patients who are benefiting from this important life-saving research. The stories that we will hear from some of the patients will 

2 

truly be astounding. They are miraculous. We all agree on the need 

to work hard toward a cure for the diseases that plague humanity, 

and we’re going to be listening to some of that success here today. 

Now, rather than discussing this, I’d like to take advantage of 

the panels that we have here today to testify. I want to turn to our 

first panel of people to testify. And they are Dr. David Hess, M.D., 

Chairman and Professor, Department of Neurology, Medical College of Georgia, in Augusta, Georgia; Dr. Joanne Kurtzberg, M.D., 

Director of the Pediatric Stem Cell Transplant Program at Duke 

University Medical Center, in Durham, North Carolina—being a 

KU grad, I’m familiar with Duke—— 

[Laughter.] 

Senator BROWNBACK.—and a very good school, other than in basketball—— 

[Laughter.] 

Senator BROWNBACK.—Dr. John W. McDonald, M.D., Ph.D., 

Washington University School of Medicine, Department of Neurology, in St. Louis, Missouri; Dr. Jean Peduzzi-Nelson, Ph.D., University of Alabama at Birmingham; and Dr. Pablo Rubinstein, 

M.D., Director of Placental Blood Program, New York Blood Center, New York, New York. 

I’m delighted to have such a distinguished panel here with us 

today to testify. I look forward to your testimony. If you would, we 

will run the clock on 7 minutes. We will take your full testimony 

into the record. I think it’s always best for people to summarize 

somewhat in putting it forward, so it can save time, as well, for 

questions afterwards. 

We do have an active floor running today. We may have to have 

recesses periodically, for me to go over and vote. Other members 

will probably be joining us, as well, so there may be some people 

stepping in. 

[The prepared statement of Senator Brownback follows:] 

PREPARED STATEMENT OF HON. SAM BROWNBACK, U.S. SENATOR FROM KANSAS

Thank you for coming to our hearing today. 

Today, we will be conducting a hearing on some of the exciting new advances 

being made in the fields of adult and non-embryonic stem cell research. 

As I am sure many of you here know, the field of regenerative medicine offers 

great hope to those suffering from disease. Much of the research that is providing 

new hope to those who are currently suffering is moving along at a fast pace and 

is doing so without questionable or morally controversial techniques. 

At this hearing we will examine some of these advances. 

This hearing is not about human cloning, or destructive human embryonic stem 

cell research. 

Rather, it is about some of the other important scientific discoveries that are 

being made using non-controversial techniques that rely on adult or non-embryonic 

stem cells. 

In particular, today we will hear from cord blood stem cell researchers as well as 

others who are working hard in the field of regenerative medicine to find the cures 

to the diseases that plague humanity. 

At this hearing we will discuss not only some of the research that is being conducted but also some of the treatments that are currently being offered. 

And, we will hear from some of the patients who are benefitting from this important life-saving research. The stories that we will hear from some of the patients 

will truly be astounding. 

Regardless of how the members of this committee feel on the controversial issues 

of human cloning and destructive human embryonic stem cell research, certainly, 

we can all agree on the need to work hard toward a cure for the diseases that 

plague humanity. 

3 

Now, rather than describe some of the advances being made I would like to turn 

to our first panel. 

Senator BROWNBACK.With that, Dr. Hess, I’d like to invite your 

testimony, and we will move on down this panel list. 

STATEMENT OF DAVID C. HESS, PROFESSOR AND CHAIRMAN, 

DEPARTMENT OF NEUROLOGY, MEDICAL COLLEGE OF 

GEORGIA 

Dr. HESS. Thank you, Senator Brownback. 

I’m David C. Hess. I’m Professor and Chairman of the Department of Neurology at the Medical College of Georgia. I am a physician and neurologist, and that’s a specialist that cares for people 

with neurological diseases. 

Many neurological diseases, such as strokes, spinal-cord injury, 

Alzheimer’s disease, Parkinson’s disease, and Lou Gehrig’s disease, 

are formidable foes, resistant to treatment, and take an enormous 

toll in suffering, like you mentioned. A week will not pass when I 

do not receive an e-mail or a call from a suffering patient asking 

for a stem cell injection to help them recover their ability to walk 

or to speak. Some patients are so desperate that they offer up 

themselves to be the first patient to try the stem cells. I can’t 

blame them. There are few effective treatments for their diseases, 

and they are looking for any ray of hope. 

As you mentioned, Senator Brownback, there is some foundation 

for their hope. The field of regenerative medicine is taking off, and 

there are new regenerative-medicine and stem cell institutes and 

centers being established all over the country. 

Many scientific dogma have been slain in the past 5 years. One 

dogma was that we don’t make new brain cells in our brain, in 

adults. In other words, you steadily lose what you have. However, 

in a set of clever experiments, it has recently been shown that humans, even in their 60s and 70s, can make new nerve cells in their 

hippocampus, a comforting fact for all of us. 

Adult stem cells can be obtained from a variety of organs, ranging from the brain’s so-called neural stem cells to the skin. However, the best study is that most accessible adult stem cells are in 

the bone marrow. Bone marrow is a rich source of stem and progenitor cells. I will briefly review the potential of adult stem cells 

derived from the bone marrow. 

As a physician, my motivation is to see some of these cells used 

to treat these devastating neurological diseases that I see every 

day. And as a physician researcher, I’m trying to make some small 

contribution to the stroke-recovery field, thanks to past support 

from the American Heart Association and, presently, the NIH. 

Let me explain. Bone marrow contains two major types of stem 

or progenitor cells, and maybe many more. The two major types are 

the hematopoietic stem cells and the mesenchymal stem cells, or 

what are often called marrow stromal cells. 

Hematopoietic stem cells have been used for years in bone-marrow transplants and have cured thousands of patients with leukemias and other forms of cancer. These hematopoietic stem cells 

have the ability to circulate throughout the whole body and reach 

every organ in the body. Their plasticity—that is, their ability to 

turn into other cell types of cells, such as nerve cells, liver cells, 

4 

and pancreas cells that produce insulin—is still hotly debated; however, there is evidence that these cells can turn into Purkinje cells 

in the brain, a very sophisticated type of nerve cell. And this phenomena is not just restricted to rodents. There is now autopsy evidence from humans that bone-marrow cells can form new neurons 

in the brain. There may also be other bone-marrow-derived cells 

that circulate in the peripheral blood, with stem cell or progenitor 

cell qualities. 

Recently, the progeny, or the daughter, of the hematopoietic stem 

cell, so to speak, circulating blood monocytes, have been shown to 

be able to differentiate into nerve cells and blood-vessel cells called 

endothelial cells. This is potentially of great clinical relevance, as 

monocytes are easy to isolate from human blood and could be a rich 

source of replacement cells. 

There are also bone-marrow cells that do not normally circulate 

in the bloodstream, but, instead, reside in the bone marrow and 

service supporting cells for the hematopoietic stem cells. These 

cells are called mesenchymal stem cells, or marrow stromal cells. 

It is these cells that are the source of much excitement in the field 

of regenerative medicine. 

Some of the most exciting research, in terms of an eventual 

human clinical application, are the multipotent adult progenitor 

cells isolated by Catherine Verfaillie. These can be isolated from 

both rodent and human bone marrow. They are able to turn into 

cells of all three germ layers. That is, they can turn into endothelial cells, which line the blood vessels, liver cells, and nerve 

cells. And, importantly, they don’t just do this in a petri dish; they 

are also able to do it in the live animal. Moreover, they do not die 

prematurely, and, importantly, they do not form teratomas, or tumors, like embryonic stem cells tend to do. 

Dr. Walter Low, a collaborator of Dr. Verfaillie, has recently 

shown that these MAPCs can aid in brain repair after stroke in a 

rodent. The obvious advantage of these cells for regenerative medicine is that they can be easily isolated from human bone marrow 

and the potential for a patient to be cured or treated with their 

own cells, without any fear of rejection. 

A closely related cell type is the marrow stromal cell. Marrow 

stromal cells have been shown to be involved in brain repair after 

stroke and traumatic brain injury, by Dr. Michael Chopp, at Henry 

Ford Hospital, and to repair the injured spinal cord, by Dr. Darwin 

Prockop’s group at Tulane. Like many other adult stem cells, these 

cells can be delivered intravenously, and they can home to the injured tissue, almost like a guided missile. There appear to be chemical signals released by injured tissue that attract these cells. Marrow stromal cells are easy to culture, easy to expand; and, since 

they can be autologous, they would not be rejected. 

How, exactly, these cells repair injured tissue is not clear. While, 

in some cases, there is actual replacement of injured cells, it seems 

more likely that these cells serve as growth-factor factories and aid 

the tissue to repair itself. 

There’s also another type of circulating bone-marrow-derived cell, 

the so-called endothelial progenitor cell that has attracted much recent interest. EPCs circulate in the bloodstream and form new endothelial cells in blood vessels. We now know that these EPCs conVerDate Nov 24 2008 06:41 May 20, 2013 Jkt 075679 PO 00000 Frm 00008 Fmt 6633 Sfmt 6601 S:\GPO\DOCS\80903.TXT JACKIE
5 

tribute to organ repair after cutting off blood supply to the heart, 

the limbs, and the brain. This is critically important, as cardiovascular disease and stroke are two of the three biggest killers in 

the United States. We have learned that by giving animals extra 

doses of these EPCs, we can improve their outcome from heart attack and salvage their limbs that are starved for blood. 

The field is moving very, very fast. Bone-marrow-derived cells 

are already being tested in small numbers of patients with heart 

attacks. The TOPCARE trial was a trial published in the journal, 

The Lancet. And, in this, bone-marrow cells, harvested from the 

patient’s own bone marrow or their blood, were delivered via a 

catheter in the coronary artery to these patients. The procedure 

was safe, and the initial results were encouraging, though this was 

a very small trial. 

Another type of bone-marrow blood stem cell, which you’re going 

to hear about later, is the human umbilical cord stem cell. These 

are derived from umbilical cords that are normally discarded after 

a delivery. Umbilical cord blood is a rich source of stem cells. These 

have already been exploited as a source of bone-marrow transplants in the cancer field and in sickle-cell anemia. 

These umbilical cord stem cells also have great potential as a 

treatment for neurological disease. When delivered intravenously to 

a rodent with a stroke, they help improve the outcome of that 

stroke in that rodent. 

Despite these hopeful signs, much work needs to be done. Before 

we are able to treat humans safely and effectively, we need to define the optimal dosing of these cells, the optimal type of bone-marrow populations to use, and the timing of when to administer them. 

And then how should we administer them? Should we give them 

directly into the tissue, like into the heart or the brain? Should we 

deliver them intravenously, or should we give them in an artery? 

There’s multiple avenues that we could give them. We also need to 

learn more about how these bone-marrow cells and other adult 

stem cells home or go to the damaged tissue. 

The major advantages of bone-marrow-derived stem cells are 

that they are autologous, with the exception of umbilical cord stem 

cells, and, therefore, they are less likely to be rejected. They can 

be easily isolated from bone-marrow aspirates, which are done 

clinically, and they avoid the ethical concerns that many have with 

embryonic stem cells. 

However, we have to keep in mind that repairing the central 

nervous system is a daunting task. Neurons make tens of thousands of connections with other nerve cells. Some of them send projections, or axons, from meters—feet, literally—and it’s very important that they connect up to the other cell. 

In most of the experiments, so far, we have little evidence that 

any stem cell delivered into an adult will be able to make all these 

connections and become fully functional. It is likely that most of 

the cell transplants in the brain work by stimulating the brain to 

actually repair itself. We need to learn more about enhancing these 

self-repair processes. 

In the growing field of cell therapy, we will need to target diseases with specific cell types and approaches. One size will not fit 

all. We may need to treat some of these diseases with a combinaVerDate Nov 24 2008 06:41 May 20, 2013 Jkt 075679 PO 00000 Frm 00009 Fmt 6633 Sfmt 6601 S:\GPO\DOCS\80903.TXT JACKIE
6 

tion of both cells and different growth factors. The treatments we 

develop for Parkinson’s disease will probably be vastly different 

from those we develop for stroke. There are no magic bullets; only 

painstaking research and more funding will allow us to advance. 

Thank you. 

[The prepared statement of Dr. Hess follows:] 

PREPARED STATEMENT OF DAVID C. HESS, PROFESSOR AND CHAIRMAN, DEPARTMENT

OF NEUROLOGY, MEDICAL COLLEGE OF GEORGIA

I am David C. Hess M.D., Professor and Chairman of the Department of Neurology at the Medical College of Georgia. I am a physician and neurologist, a specialist that cares for people with neurological diseases. Many neurological diseases 

such as stroke, spinal cord injury, Alzheimer’s disease, Parkinson’s disease, and 

Amyotrophic Lateral Sclerosis (Lou Gehrig’s disease) are formidable foes, resistant 

to treatment and take an enormous toll in suffering. A week will not pass when I 

do not receive an e-mail or a call from a suffering patient asking for a stem cell 

injection to help them recover their ability to walk or speak.. Some patients are so 

desperate that they offer up themselves to be the first patient to try the stem cells. 

I can’t blame them; there are few effective treatment for their diseases and they are 

looking for any ray of hope. They have also been influenced by exaggerations in the 

media. 

Yet there is some foundation to their hope. The field of ‘‘regenerative medicine’’ 

is taking off and there are new ‘‘Regenerative Medicine’’ and ‘‘Stem Cell’’ institutes 

and centers being established all over the country. Many scientific dogma have been 

slain in the past 5 years. One dogma was that new neurons are not born in the 

brains of humans-in other words, you just steadily lose what you have as you age. 

However, in a set of clever experiments by Drs. Ericksson and Gage in1998 it was 

shown that humans even in their 60s can make new nerve cells in their hippocampus, a comforting fact for all of us. Moreover, mice make more new neurons if 

they are kept in an ‘‘enriched’’ environment and exercise (Kempermann, 2002). If 

we can extrapolate these findings to humans, it suggests that by keeping our minds 

active we are less likely to lose them. We also now know that new neurons can be 

made in response to a brain injury in other parts of the rodent brain, not just the 

hippocampus. For example, after a stroke, new neurons are born and travel to the 

damaged tissue and appear to aid in its repair (Arvidsson, 2002). Now we have to 

learn how to enhance and stimulate these natural repair mechanisms. 

Adult stem cells can be obtained from a variety of organs ranging from the brain 

(so called neural stem cells) to the skin. However, the best studied and most accessible adult stem cells are in the bone marrow. Bone marrow is a rich source of stem 

and progenitor cells. I will briefly review the potential of adult or non-embryonic 

stem cells to treat human disease. I will focus on bone marrow stem cells. As a physician my perspective is on the clinical potential of these advances and my motivation is to see some of these cells used to treat these devastating neurological diseases that I see every day. As a physician-researcher, I am trying to make some 

small contributions to the stroke recovery field thanks to past support from the 

American Heart Association and currently the NIH. 

Bone marrow contains two major types of stem or progenitor cells and maybe 

many more. The two major types are the hematopoietic stem cells and the 

mesenchymal stem cells or marrow stromal cells. Hematopoieitc stem cells have 

been used for years in bone marrow transplants and have cured thousands of patients with leukemias and other forms of cancer. These hematopoietic stem cells and 

their progeny-the white blood cells, red blood cells and platelets-have the ability to 

circulate throughout the bloodstream and reach every organ in the body. Their plasticity, that is, the ability of these cells to ‘‘turn ‘‘into other cell types such as nerve 

cells, liver cells and pancreas cells that produce insulin, is still hotly debated. However, there is evidence that these cells can rarely differentiate into Purkinje cells 

in the brain, a very sophisticated type of neuron. The phenomenon is not restricted 

to rodents; there is now autopsy evidence from humans that bone marrow cells are 

involved in the formation of neurons at a low level (Mezey, 2003) 

Some recent evidence had suggested that cell fusion was responsible for some of 

the plasticity that had been described for bone marrow stem cells (Terada, 2002; 

Wang, 2003; Vassilopoulos, 2003). In cell fusion, the bone marrow cells would not 

actually ‘‘turn into’’ another cell type-they would just fuse with the mature cell giving it twice the number of chromosomes and thereby making it potentially unstable. 

However, while cell fusion may indeed account for some of the ‘‘plasticity’’ of bone 

7 

marrow cells, particularly in the liver, it does not seem to account for all of it. In 

recent work, bone marrow cells have been shown to become functional insulin-secreting cells in the pancreas of mice without any evidence of cell fusion (Ianus, 

2003). 

There may also be bone marrow-derived cells that circulate in the peripheral 

blood with ‘‘stem cell’’ or ‘‘progenitor cell’’ qualities. Recently the progeny of the 

hematopoietic stem cell, a subpopulation of circulating blood monocytes, have been 

shown to be able to differentiate into nerve cells and blood vessel cells called endothelial cells (Zhao, 2003). This is potentially of great clinical relevance as monocytes 

are easy to isolate from human blood and could be a rich source of replacement cells. 

There are also bone marrow cells that do not normally circulate in the bloodstream but instead reside in the bone marrow and serve as supporting cells for the 

hematopoietic stem cells. These cells are called mesenchymal stem cells or marrow 

stromal cells. It is these cells that are the source of much excitement in the field 

of regenerative medicine. Some of the most exciting research, in terms of an eventual human clinical application, are the Multipotent adult progenitor cells (MAPC) 

isolated by Catherine Verfailie and described comprehensively in the July 2002 

issue of Nature (Jiang, 2002). These cells can be isolated from rodent and human 

bone marrow. They are able to differentiate into cells of all three germ layers 

(endoderm, mesoderm and ectoderm) that is they can from endothelial cells or blood 

vessel lining cells, hepatocytes (liver cells), and nerve cells. They not only do this 

in the petri dish, they also do it in the live animal. Moreover, they do not senesce 

or die prematurely and importantly they do not form teratomas or tumors like embryonic stem cells tend to do. Dr. Walter Low a collaborater of Dr. Verfaillie has 

shown that these MAPCS can aid in brain repair after stroke in a rodent (Zhao, 

2002). The obvious advantages of these cells for regenerative medicine is their easy 

isolation from human bone marrow and the potential for a patient to be their own 

donor without fear of rejection. 

A closely related cell type is the marrow stromal cell. Marrow stromal cells have 

been shown to be involved in brain repair after stroke and traumatic brain injury 

by Dr. Chopp at Henry Ford Hospital and to repair the injured spinal by Dr. Darwin 

Prockop’s group at Tulane. Like many other adult stem cells, these cells can be delivered intravenously and then ‘‘home’’ like a guided missile to the injured tissue. 

There are chemical signals released by injured tissue that attract these cells. Marrow stromal cells are easy to culture, easy to expand, and since they are autologous 

they would not be rejected. How exactly these cells repair injured tissue is not clear. 

While in some cases this is actual replacement of damaged cells, it seems more likely that these cells serve as growth factor ‘‘factories’’ and aid the tissue to repair 

itself by reactivating latent developmental programs. 

There is also another type of circulating bone marrow-derived cell, the endothelial 

progenitor cell (EPC) that has also attracted much recent interest. Endothelial cells 

are cells that line all the blood vessels of the body. Besides being mere conduits for 

blood, we now know that they play an active and necessary role in the development 

and sustenance of the body’s organs. Bone marrow cells that can circulate in the 

bloodstream and form new endothelial cells and blood vessels were first described 

and characterized in 1997 (Asahara). We now know that these EPCS contribute to 

vessel and organ repair after ischemia to the heart, limbs and brain (Rafii, 2003). 

This is critically important as cardiovascular disease and stroke are two of the three 

biggest killers in the U.S. We have learned that by giving animials extra doses of 

these EPCS, we can improve their outcome from heart attack and salvage their 

limbs that are starved for blood.. Also, these EPCs can be mobllized from the bone 

marrow and into the peripheral blood with drugs and different growth factors . 

Some of these growths such G–CSF are already approved by the FDA for other indications 

The field is moving fast. Bone marrow-derived stem cells are already being tested 

in small numbers of patients with heart attacks. In the TOPCARE trial, bone marrow cells harvested from the same patient’s bone marrow or their blood were delivered via a catheter in the coronary artery to injured heart tissue (Assmus, 2002). 

The procedure was safe and initial results were encouraging. There is also a trial 

using bone marrow cells in patients with congestive heart failure (Perin, 2003). 

Another type of bone marrow or blood stem cell is the human umbilical cord stem 

cell. These are derived from umbilical cords that are normally discarded after a delivery. Umbilical cord blood is a rich source of stem cells. These have already been 

exploited as a source of bone marrow transplants in the cancer field. These umbilical cord stem cells also have great potential as a treatment for neurological diseases. When delivered intravenously to a rodent with a stroke, they help improve 

the recovery from the stroke (Chen, 2001). 

8 

Despite these hopeful signs, much work needs to be done. Before we are able to 

treat humans safely and effectively, we need to define the optimal dosing of these 

cells, the optimal type of bone marrow populations to use, the timing of when to 

administer, and the best route of administration (inject directly into the organ, intravenously, intra-arterially). We also need to learn more about how they these bone 

marrow cells and other adult stem cells home to damaged tissue so we can exploit 

this therapeutically. 

The major advantages of bone marrow derived stem cells are: 1) they are 

autologous (except for umbilical cord stem cells) and will not be rejected; 2) they can 

be easily isolated from bone marrow aspirates; and 3) they avoid the ethical concerns that many have with embryonic stem cells. However, we also have to keep 

in mind that repairing the nervous system is a daunting task. Neurons make tens 

of thousands of connections with other neurons. Some send their projections (axons) 

for meters and then connect to another cell. In most of the experiments so far we 

have little evidence that stem cells delivered into an adult will be able to make all 

these connections and become fully functional. It is likely that most of the cell transplants in the brain work by stimulating the brain to repair itself. We need to learn 

more about enhancing these endogenous (self) repair processes. In this growing field 

of ‘‘Cell Therapy’’, we will need to target diseases with specific cell types and approaches-one size will not fit all. We may need to treat some of these diseases with 

a combination of both ‘‘cells’’ and growth factors. The treatments we develop for Parkinson’s disease will be different from those we develop for stroke. There are no 

magic bullets-only painstaking research will allow us to advance. 

References 

Arvidsson A., Collin T., Kirik D., Kokaia Z., Lindvall O. Neuronal replacement 

from endogenous precursors in the adult brain after stroke. Nat Med. 2002 Sep; 

8(9):963–70. 

Asahara T., Murohara T., Sullivan A., Silver M., van der Zee R., Li T., 

Witzenbichler B., Schatteman G., Isner J.M. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997 Feb 14; 275(5302):964–7. Assmus B., 

Schachinger V., Teupe C., Britten M., Lehmann R., Dobert N., Grunwald F., Aicher 

A., Urbich C., Martin H., Hoelzer D., Dimmeler S., Zeiher A.M.; Transplantation of 

Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction.Transplantation of Progenitor Cells and Regeneration Enhancement in Acute 

Myocardial Infarction (TOPCARE–AMI). Circulation. 2002 Dec 10; 106(24):3009–17. 

Chen J., Zhang Z.G., Li Y., Wang L., Xu Y.X., Gautam S.C., Lu M., Zhu Z., Chopp 

M. Intravenous administration of human bone marrow stromal cells induces 

angiogenesis in the ischemic boundary zone after stroke in rats. Circ Res. 2003 Apr 

4; 92(6):692–9 

Chen J., Sanberg P.R., Li Y., Wang L., Lu M., Willing A.E., Sanchez-Ramos J., 

Chopp M.Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke. 2001 Nov; 32(11):2682–8. 

Eriksson P.S., Perfilieva E., Bjork-Eriksson T., Alborn A.M., Nordborg C., Peterson D.A., Gage F.H.. Neurogenesis in the adult human hippocampus. Nat Med. 1998 

Nov; 4(11):1313–7 

Hofstetter C.P., Schwarz E.J., Hess D., Widenfalk J., El Manira A., Prockop D.J., 

Olson L. Marrow stromal cells form guiding strands in the injured spinal cord and 

promote recovery. Proc Natl Acad Sci USA. 2002 Feb 19; 99(4):2199–204. 

Ianus A., Holz G.G., Theise N.D., Hussain M.A.. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. 

J Clin Inest 2003 March 111(6): 843–50 

Jiang Y., Jahagirdar B.N., Reinhardt R.L., Schwartz R.E., Keene C.D., Ortiz-Gonzalez X.R., Reyes M., Lenvik T., Lund T., Blackstad M., Du J., Aldrich S., Lisberg 

A., Low W.C., Largaespada D.A., Verfaillie C.M. Pluripotency of mesenchymal stem 

cells derived from adult marrow.. Nature 2002 Jul 4; 418(6893):41–9 

Kempermann G., Gast D., Gage F.H. Neuroplasticity in old age: sustained fivefold 

induction of hippocampal neurogenesis by long-term environmental enrichment. Ann 

Neurol. 2002 Aug; 52(2):135–43. 

Li Y., Chen J., Chen X.G., Wang L., Gautam S.C., Xu Y.X., Katakowski M., Zhang 

L.J., Lu M., Janakiraman N., Chopp M.. Human marrow stromal cell therapy for 

stroke in rat: neurotrophins and functional recovery. Neurology. 2002 Aug 27; 

59(4):514–23 Mezey E., Key S., Vogelsang G., Szalayova I., Lange G.D., Crain B. 

Transplanted bone marrow generates new neurons in human brains. Proc Natl Acad 

Sci USA. 2003 Feb 4; 100(3):1364–9 Perin E.C., Geng Y.J., Willerson J.T. Adult 

stem cell therapy in perspective. Circulation. 2003 Feb 25; 107(7):935–8. 

Rafii S., Lyden D. Therapeutic stem and progenitor cell transplantation for organ 

vascularization and regeneration. Nat Med. 2003 Jun; 9(6):702–12. 

9 

Terada N., Hamazaki T., Oka M., Hoki M., Mastalerz D.M., Nakano Y., Meyer 

E.M., Morel L., Petersen B.E., Scott E.W.. Bone marrow cells adopt the phenotype 

of other cells by spontaneous cell fusion. Nature. 2002 Apr 4; 416(6880):542–5 

Vassilopoulos G., Wang P.R., Russell D.W.. Transplanted bone marrow regenerates 

liver by cell fusion. Nature. 2003 Apr 24; 422(6934):901–4 Wang X., Willenbring H., 

Akkari Y., Torimaru Y., Foster M., Al-Dhalimy M., Lagasse E., Finegold M., Olson 

S., Grompe M.. Cell fusion is the principal source of bone-marrow-derived 

hepatocytes. Nature. 2003 Apr 24; 422(6934):897–901 

Zhao L.R., Duan W.M., Reyes M., Keene C.D., Verfaillie C.M., Low W.C.. Human 

bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol. 2002 Mar; 174(1):11– 

20. Zhao Y., Glesne D., Huberman E. A human peripheral blood monocyte-derived 

subset acts as pluripotent stem cells. Proc Natl Acad Sci USA 2003 Mar 4; 

100(5):2426–31 

Senator BROWNBACK. What you’re describing is exciting and I 

hope this is a field that we can put much additional research funding into. 

Dr. Rubinstein, thank you very much for joining us today. 

STATEMENT OF PABLO RUBINSTEIN, M.D., DIRECTOR OF 

PLACENTAL BLOOD PROGRAM, NEW YORK BLOOD CENTER 

Dr. RUBINSTEIN. Thank you very much, Senator. We are grateful 

for the opportunity to address this Committee. 

The work I will describe refers to the stem cells that are present 

in cord blood. This work, which will be presented by both myself 

and Dr. Kurtzberg, has taken place over a number of years, as I 

will describe. 

The first evidence that there were stem cells in cord blood was 

reported in 1974. From that time to the present, the most important elements in this history are the first cord-blood transplant 

that occurred in 1988. During the intervening years, there was a 

lot of research done that allowed this to happen. From 1988, where 

the first patient was transplanted by—a patient from Duke University, a patient of Dr. Kurtzberg’s. 

The next big element was the setting up of a cord-blood program 

for treating patients without sibling donors, where we collect cord 

blood from unrelated donors, with informed consent, and this blood 

is frozen and then is available for use on anyone who needs them. 

The first unrelated cord-blood transplant from our repository at 

New York Blood Center was performed by Dr. Kurtzberg at Duke 

in 1993. 

And the next step in this story is the exemption granted by the 

FDA for us to continue this research and to expand the range of 

documented indices of the activities of these transplants. This year, 

there have been more than 3,500 transplants performed worldwide, 

so far, with cord blood. Of these, more than 2,000 have been in the 

United States, and 1,370 from our own cord-blood bank. 

The NIH has recognized the importance of this work and has created a second study, the COBLT study, which Dr. Kurtzberg participated, both of the transplanted and as a banker, to produce 

more of these transplants for patients in need. Dr. Kurtzberg will 

also report beautiful results that have been obtained with patients 

with cord-blood transplants that repaired, or at least helped to repair, tissues other than the blood and the immune system, which 

are a direct province of the stem cells in the cord blood. 

10 

How is cord blood prepared and used? After the birth of a 

healthy baby, the placenta is removed, with the major segment of 

the cord, and the baby goes one way; the placenta is taken out. 

Normally, this placenta, with the segment of the cord, is discarded. 

In our case, we drain the blood that is left in the placenta, and we 

take it to the laboratory, process it, freeze it down, and, as the slide 

shows, we have special containers that allow us to freeze it in liquid nitrogen. At the temperature of liquid nitrogen, this blood will 

be available for transplantation for many years, without attrition. 

The blood is stored in special containers, which maintain control 

and information, directly in the same device. 

Results that have been obtained in the clinical use of this cord 

blood over the years allow us to compile a list of advantages that 

cord blood offers to clinicians and patients, in comparison with 

bone marrow. There are, first of all, no risks to the donors. There 

is no donor attrition. The blood will stay frozen until it’s used. If 

it is processed correctly, it will be available for many years. We 

don’t know how many, because it’s longer than has been used, so 

far over 15 years. Grafts are available on short notice. They can be 

produced, and routinely are produced, in our case, within days, not 

months or years. There are fewer latent viral infections in cord 

blood than in adult bone marrow. 

But the main reason why this blood is so important is because 

the immune reaction that the donor’s cells exert against the recipient’s tissues, which is a problem with bone-marrow transplantation, is much weaker in the case of cord blood; probably reflecting 

the biological status of that blood that comes from an organism in 

which the mother and the child have to tolerate each other. This 

advantage allows us to perform transplants with some mismatches. 

In bone-marrow transplantation, the more mismatches, the more 

problems occur for the patient; not just immediate, but for a long 

time for those patients who are successfully treated. 

That allows us, therefore, to find matches for people who have 

very much difficulty finding matches, people with rare types and 

people of ethnic minorities in which the opportunities to find a 

donor among those in the volunteer donor groups is much less, simply because there are fewer of them in the population. 

Another important result, which is now being shown in the slide, 

has been obtained in cooperation with the International Bone Marrow Transplant Registry. Several hundred patients transplanted 

with bone marrow were compared with cord-blood recipients for the 

same disease and the same age groups. The cord blood with no 

more than one mismatch, and the bone marrow with no more than 

one mismatch, as you can see offer exactly the same long-term 

transplant survival. What you’re not seeing here is that the clinical 

condition of the patients is different. The cord-blood recipients usually have a much easier time, with much fewer chronic graft versus 

host disease than the bone marrow. 

Another thing the slide doesn’t show is that the average result 

for all types of transplants that are taking place. And in the case 

cord blood, there is an additional influence. In addition to the 

matching is the cell dose. You can see, in the panel on the left, that 

people transplanted with small cell doses have a lower probability 

of long-term survival. But if we can eliminate, from our transplanVerDate Nov 24 2008 06:41 May 20, 2013 Jkt 075679 PO 00000 Frm 00014 Fmt 6633 Sfmt 6601 S:\GPO\DOCS\80903.TXT JACKIE
11 

tation, the need to use those small cord bloods, we can shift the 

whole curve up and offer an overall larger probability of success. 

To terminate, I would just like to show you two slides, which 

refer to the need. It has been reported by the GAO, in October last 

year, the situation with bone-marrow transplantation that reflects 

the fact that in this country, at the moment, for people who need 

unrelated transplants, the opportunity to get the transplant is estimated at about 9 percent of the total. For the period 1997 to 2000, 

of an estimated 44,000 patients who needed transplant, 4,056 got 

them—10 percent of the need, and about a quarter of all of those 

patients that went all the way to search officially. 

Finally, the other aspect of cord blood is, because of its tolerance 

of mismatches, it’s possible to transplant patients of the different 

minority populations in our country with appropriate transplants. 

And, in this slide, you can see four populations—Asians, African 

Americans, Hispanic, and Caucasians. The African American is 

highlighted as an example. You will see, in the first part of the 

slide, that the proportion of African Americans, among all those 

who search, is about 12 percent, which reflects very closely with 

the size of the African American community in the national scope. 

However, the donors that were transplanted with bone-marrow 

transplants by the NMDP is only 6 percent, so only half as much 

chance as is available if they were equally—if they have equal access to the transplants. With cord blood, however, the probability 

is 19 percent. And the reason for that is twofold. One is that we 

can make transplants that are less well matched. And, second, that 

we can select our donors by harvesting the cord blood in places 

where we can collect effectively, cord blood from members of these 

ethnic, and all the ethnic, groups. And, as a result, we can improve 

the access of these patients to transplantation. 

This is my part of the presentation. And now Dr. Kurtzberg will 

continue. 

Senator BROWNBACK. Thank you very much, Dr. Rubinstein. 

And, Dr. Kurtzberg, I look forward to your testimony here today. 

STATEMENT OF JOANNE KURTZBERG, M.D., DIRECTOR, 

PEDIATRIC STEM CELL TRANSPLANT PROGRAM, 

DUKE UNIVERSITY MEDICAL CENTER 

Dr. KURTZBERG. We’re going to have a little technical switch 

here. 

Senator BROWNBACK. All right. 

Dr. KURTZBERG. OK. 

Well, thank you very much for listening to our story today about 

cord blood. I’m going to continue by talking about the clinical applications of cord-blood transplantation, today and in the future. 

We’ve been very excited about cord-blood transplantation, because, as a transplant physician, I, and all others, are faced with 

patients who need the therapy and don’t have donors. And cord 

blood has filled the niche for those patients, because it can be used 

without complete matching. 

Now, the child shown in this slide was the first recipient ever of 

a cord-blood transplant. He’s from Salisbury, North Carolina, and 

was transplanted in 1988 with cord blood from his baby sister. And 

his transplant was extremely important, because there was no way 

12 

to really demonstrate or prove, in animal model or in a test tube, 

that cord blood contains sufficient numbers of stem cells to reconstitute a patient. And there were many skeptics, and most people 

believed it wouldn’t work. But this family was very courageous and 

allows his baby sister’s cord blood to be used for his transplant for 

a rare genetic diseased, called Fanconi anemia. And he’s shown—— 

Senator BROWNBACK. What was the disease? 

Dr. KURTZBERG. Fanconi anemia, which is an inherited disease 

that causes death in the first decade of life. It’s a defect in DNA 

repair. And it affects all cells in the body; but first, the blood. And 

it leads to bone-marrow failure, or leukemia, causing death in the 

first decade of life. 

Senator BROWNBACK. Thank you. 

Dr. KURTZBERG. This boy was successfully transplanted, successfully engrafted, is shown 15 years later, in the right-hand panel, 

and is doing well; well, has a durable graft. Again, one of the questions a transplanter would have is, ‘‘Will the cells not only grow 

back at the beginning, but will they stay there, and will they remain and grow with the patient who received them?’’ And he is the 

longest living survivor of a cord-blood transplant, the first recipient 

of a cord-blood transplant. And, at least at 15 years, we can say 

that this is a durable graft, without causing any late problems. 

Now, after his transplant, there were other related transplants 

performed in small numbers over the next 5 years, but the real 

breakthrough in cord-blood transplantation came when Dr. Rubinstein’s bank was established and there was a pool of donors in the 

unrelated setting. And it’s now been shown that cord blood can be 

used for all the applications of bone marrow and that includes 

those listed in the slide—hematologic malignancies, immune deficiencies, like the ‘‘bubble boy’’ disease, marrow-failure syndromes, 

hemoglobinopathies. And you’ll hear from a sickle-cell anemia patient later, who has had his disease corrected with a cord-blood 

transplant. 

And then a very interesting category of diseases called the ‘‘inborn errors of metabolism,’’ where babies are born missing enzymes 

that are necessary for development of the brain or the muscles or 

the heart or the skeletal system; and where, without therapy, they 

generally die in infancy or early childhood. 

Now, I only have time to show you a little bit of data from patients transplanted with cord blood; and I chose the genetic diseases to focus on, because I think they really illustrate lessons that 

we can learn to move into the field of regenerative medicine. 

This slide shows our results transplanting children with genetic 

immunodeficiency syndromes—where their immune system is absent at birth. And there are multiple forms of this disease. It’s fatal 

in childhood, without treatment, either because of infection or cancer. And transplant is the only therapy that’s curative. 

This little boy was transplanted at 18 months of age, when he 

was critically ill with a fungal infection, and really no one thought 

he would even make it through the transplant. And he’s shown 3 

years after transplant, successfully corrected with a normal immune system. 

Overall, in about 30 patients with this disease, we have an 80 

percent event-free survival, which is shown in that curve. And 

13 

what that means is these children are alive, well, engrafted, and 

they have a recovered immune system that functions normally. 

Senator BROWNBACK. And the children would have all died. 

Dr. KURTZBERG. They would have all died, yes. These are lethal 

genetic conditions. 

Another example is an inborn error called Hurler syndrome, 

where children are born missing an enzyme that’s necessary for development of the brain, the liver, the bones, the cornea, and the 

cartilage. And this little girl is an example of a child transplanted 

with Hurler in infancy. These children generally die by the age of 

five to 10 years. And although they have severe mental retardation, 

they actually die of atherosclerotic heart disease because of deposits that fill up the coronary arteries and cause damage to the heart 

muscle. And transplant, again, will correct this disease. And, in our 

hands, transplanting now over 25 children, the event-free survival 

is 90 percent. That means these children are engrafted, corrected. 

And I just showed you one example of a child transplanted at 5 

months of age, now 6 years old, with a normal IQ—actually, a high 

IQ—and she’s a reflection, not an exception. All the children we’ve 

treated have had normal development and regained skills that they 

had lost. 

Senator BROWNBACK. And normal IQ development. 

Dr. KURTZBERG. Yes, they are in the normal range. 

We also know that their bones have corrected, and that they 

have not developed coronary artery disease, which probably has implications for adult coronary artery disease, although the pathogenesis is different. 

A third disease that really falls into a category called leukodystrophy, where there’s, again, children born with defects in 

myelination. Myelin is the covering of the nerve sheath in the 

white matter of the brain. And without that covering, the brain 

neurons are damaged and die. Krabbe disease is the most severe 

leukodystrophy, with the earliest onset, and children who have this 

disease generally develop normally for the first few months of life 

and then regress and are vegetative by a year of age, and die between one and two years of age. 

Now, the little boy in the picture lost a sibling to Krabbe disease, 

and the sibling died at 13 months of age. He’s shown at 2 years 

of age, but he was transplanted at 3 weeks of age, because we 

knew, the cause of his sibling’s death we know to look for the disease. And when he was diagnosed, we were able to mobilize a cord 

blood within a few days. We tested that cord blood to make sure 

that cord blood didn’t carry the disease, and then go forward with 

a transplant in the first month of life. There have now been ten 

children treated in the United States with that same approach, and 

all ten are doing very well anywhere from one to 6 years later. 

The survival curves that are portrayed on the graph show you 

that the newborn transplants, which is the top of the line and is 

straight, at 100 percent, all are surviving, doing well, and developing normally. Children in the middle line, that goes down and 

evens out at about 40 percent, are children who had no family history. There was no way to know to look for the disease. They were 

diagnosed after they had symptoms, and they had some brain damage at that point. And those children have a 40 percent event-free 

14 

survival, and they are left with some disability, sometimes severe 

and sometimes mild. 

Senator BROWNBACK. So the age that you catch this is very significant. 

Dr. KURTZBERG. Well, it’s either the age or the amount of damage or both, and it’s hard to know. 

And then the other line, that goes all the way down to zero, 

shows you the natural history of the disease in untreated children. 

In this case, there are 156 in the curve. And these are children 

whose families contacted us, and we evaluated, but we felt were too 

advanced with the disease for the procedure, and so they were not 

treated, and the disease ran its natural course. 

Now, this is an MRI picture. Now, I know it’s a little complicated, but it shows the brain of a different child, who was also 

transplanted, with Krabbe, in the first 3 weeks of life. And what’s 

interesting here is, this is her scan—moving into it with my 

arrow—at 1 year of age, the smaller brain; and then, on the lefthand panel, 2 years of age. And at 1 year of age, she has some 

fluffy stuff around the ventricles, which is inflammation, which is 

abnormal. But, at 2 years of age, that has regressed and has gone 

away. And, in addition, these gray lines show myelination, which 

is normal for age. Now, this child would not have been able to 

myelinate her brain if she had not been transplanted. And, in fact, 

she probably would not have survived to this age. But this shows 

actual repair on a scan in a child who is doing well. 

This last slide of this Krabbe story shows brain tissue from a 

child who died. The child was a girl, and she received a transplant 

from a boy. And these are nuclei of brain cells in the white matter 

and in something called the choroid plexus, which are the cells lining the ventricles. All the cells that have blue or green dots are 

male cells, donor cells, that have traveled to this child’s brain and 

distributed throughout the brain. In fact, we found that 30 to 40 

percent of the cells in her brain came from the donor, and we’re 

investigating what kinds of cells they are. 

But, again, as you think of repairing neurologic damage, this is 

a hint that maybe these cells have the capacity to do that, and they 

certainly need to be examined further. 

Finally, I want to just end with a few comments about sickle-cell 

anemia and hemoglobinopathies. Sickle-cell anemia, as you’ll hear 

later, can be cured by hematopoietic stem cell transplantation, either from bone marrow or from cord blood. But many patients don’t 

have donors. And we have transplanted a few patients with sicklecell disease and leukemia, and cured both diseases. 

The little boy in the picture here is a surgeon’s son, who has 

thalassemia, which is another kind of hemoglobinopathy, and he 

was the first recipient of a cord-blood transplant for hemoglobinopathy, at two-and-a-half months of age, before the disease had 

caused any damage to any of his organs. And he is going well, at 

5 years of age, without any symptoms or problems from the disease. 

Personally, I believe that we should be taking the same approach 

for sickle cell, using the transplant very early in childhood or infancy, where the transplant survival rates are better. This graph 

shows you event-free survival after related cord-blood transplants, 

15 

and they are 90 percent survival, and 80 percent of event-free survival in thalassemia and sickle-cell disease, respectively. And so 

this works and is better than much of the morbidity that much of 

the patients who suffer with this disease later will experience. 

Also, cord blood has a role here for African American patients, 

who otherwise can’t find donors very quickly. 

Cord blood has a lot of applications right now, in the diseases I 

mentioned and others. It also has applications, I think, in the future for cellular therapies, along with other stem cell sources. And 

our real request here is to continue to be able to bank cord blood 

in the public setting. 

And very briefly, Dr. Rubinstein told you the history, but the 

NHLBI had funded both his first public cord-blood bank, and then 

a second group of banks, under a program called COBLT. Those 

banks and Dr. Rubinstein’s bank have proven that this is an important resource. But now there’s no continued funding to take this 

resource, where really about $20 million was already expended to 

build it up and continue it. It needs to transfer over to the service 

sector and be supported through federal dollars. 

So our proposal is to establish a national cord-blood program, 

which will provide grafts for patients in need now and provide an 

inventory of cells for research and future cellular therapies, and we 

need to have funding to create a network of four to six banks in 

the United States that will network together to build an inventory 

of about 100 to 150,000 units, which are the numbers needed to 

solve the problems that Dr. Rubinstein illustrated with cell dose 

and matching. 

I’ll stop there. Thank you. 

[The prepared statement of Dr. Rubinstein and Dr. Kurtzberg 

follow:] 

CORD BLOOD

A SOURCE OF STEM AND PROGENITOR CELLS FOR PATIENTS IN NEED OFBONE

MARROW TRANSPLANTATION AND OTHER CELLULAR THERAPIES

Pablo Rubinstein, M.D., New York Blood Center and Joanne Kurtzberg, M.D., Duke University 

CORD BLOOD RESEARCH PROGRESS

• 1974: First Report on Stem/Progenitor Cells in Human Cord Blood 

• 1988: First Cord Blood Transplant (Sibling) 

• 1992: First Public Cord Blood Bank 

(Unrelated Donors. NIH-sponsored Research) 

• 1993: First Unrelated Cord Blood Transplant 

• 1996: First FDA IND + NIH Sponsored COBL T Study 

• 2003: More than 3500 Cord Blood Transplants Worldwide, 2000 in U.S. 

• 2003: Donor-type Cells of Non-Blood or Immune Lineages and Evidence of Myelin Regeneration in Patients with lysosomal storage diseases after Cord Blood Transplant 

16 


612PABLO3.eps 612PABLO4.eps

Collection, processing and archiving 

cord blood for stem cell transplantation by 

most public cord blood banks 1. After birth, cut 

cord and 

separate 

placenta 

2. Collect cord 

blood by 

gravity from 

umbilical cord 

3. Unit of 

concentrated 

stem cells 

!::=:::;:i! ;=;; 4. CryoResearch Results: 

Advantages of Cord Blood 

preservation 

& storage 

as a Clinical Source of Stem Cells 

(Compared to bone marrow) 

• Cord Blood Donation poses no risks to donors 

• No donor attrition: Well processed and stored 

grafts are good for many years 

• Grafts are available on short notice (days) 

• Less latent viral infection 

• Less immune reaction against recipient: 

(lower graft-vs.-host reaction) 

• Tolerance of mismatches: Easier to find useful 

matches for patients of all ethnic groups 
17 


612PABLO5.eps 612PABLO6.eps

The importance of CB TNC dose and 

HLA match for survival: 

80 

20 

o 

NYBC data 

US Patients - all diseases 

TNC Dose (n) 

~100 x 106/kg (n=154) 

50-99 (n=230) 

25-49 (n=339) 

< 25 (n=276) 

P<0.0001 

2 3 4 

80 

60 

20 

Years Post Transplant 

HLA Match (n) 

6/6 (n=28) 

5/6 (n=241) 

4/6 (n=417) 

< 4/6 (n=50) 

2 3 4 5 

5-Year Survival in US Children with 

Leukemia or Myelodysplasia 

co 

> 

.~ 

80 

60 

::l 40 en 

~ 

20 

o 

Data from IBMTR - NYBC stud 

Cord Blood 6/6 and 5/6 HLA Match 

P = 0.8 

1 2 3 4 

Years Post-Transplant 

5 
18 


612PABLO7.eps 612PABLO8.eps

Bone Marrow Transplantation Today 

(GAO Report, 2002) 

(NMDP data) 

1997-2000 

44,740 Patients Needed Transplants 

15,231 Preliminary NMDP Search 

9,623 Formal NMDP Searches 

4,056 Transplants 

«10% of need, 26.6% of searches) 

"Typically requires many 

months, 

Bone Marrow Transplantation: 

Ethnicity and Access to Transplants 

* NMDP data, GAO Report, 2002 ** NYBC research data 

" .. equal access to a match may "Equal access to a match is 

not be attainable. " attainable. " 

Ethnicity Searches Donors Transplants 

NMDP NYBC NMDP NYBC NMDP NYBC 

Asian 3.7% 3.6% 8% 6.7% 2.4% 4.0% 

African American 12.1% 12.1% 10% 24.6% 6.3% 19.0% 

Hispanic 12.5% 14.0% 11% 23.5% 7.8% 15.7% 

Caucasian 69.1% 67.8% 67% 45.2% 81 .9% 58.5% 
19 


612PABLO9.eps 612PABLO10.eps

First Human Cord Blood Transplant 

(Sibling) 

Matthew 1988, 

Age 6, 

Fanconi Anemia 

Matthew 2001, 

Age 19, 

Healthy, attending 

college. Durably 

eng rafted without 

adverse sequelae. 

Research Results: 

Applications of Unrelated Cord Blood 

Transplantation: 1993-2003 

• Hematologic malignancies - Leukemia, lymphoma 

• Immunodeficiency diseases - SCID, CID, CVID, WAS 

• Bone marrow failure syndromes - Fanconi Anemia, Severe aplastic anemia 

• Hemoglobinopathies 

- Sickle Cell Anemia 

- Thalassemia Major 

• Inborn errors of metabolism - ADL, MLD, GLD 

- MPS I, II, III, VI 

- Tay Sachs Disease 
20 


612PABLO11.eps 612PABLO12.eps

Genetic Immunodeficiency Disease 

Transplanted for WAS 

At age 18 months 

Event-free survival (25 patients) 

~ .~ 60 

:::I 

til 

~ 40 

20 

o 

1 Year Survival = 0.78 (SE = 0.09) 

Median Time of Follow-up = 47.5 Months 

o 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 

Mon~hs Post Transplant Shown at 3 years 

post transplant 

Patients with SCID, CID, CVID, Wiscott Adrich Syndrome, Leukocyte 

Adhesion deficiency, etc. recover full immune function (both T and 8 cells) 

after unrelated cord blood transplantation. 

80 

Metabolic Disease 

MPS-1 (Hurler Syndrome) 

Event-free survival (15 Patients) 

Transplanted with UCB 

at 5 months of age 

~ .~ 60 

::I 

rn 

?J. 40 

20 

o 6 12 18 24 30 36 42 48 54 60 66 72 78 84 

Months post transplant 

Shown at 6 years 

post transplant 

IQ147 

CB transplant arrests progression and reverses damage in the Cl rnea, 

liver, bones, cartilage, hearts and brains of young patients with Hurler 

Syndrome which otherwise causes death by 5-6 years of age. 
21 


612PABLO13.eps 612PABLO14.eps

tU 

> 

.~ 

:::I 

CIl 

~ 

Metabolic Disease 

Krabbe Disease (Globoid Leukodystrophy) 

1.0 

0.8 

0.6 

0.4 

0.2 

0.0 

0 

Overall Survival 

-r~ - - - -:::::: pr;-~ptomatlc (N=5) 

~ -- Symptomatic (N=11) 

, ----- Un1reated (N=l56) 

\ 

\\ 

"Sl~ 

~\l -ILlll_.J __ , 

-1_L_1 '-, 

12 24 36 48 60 72 84 96 

Months post transplant 

Transplanted at 3 weeks of age 

This child is now neurologically 

normal at age 5. Two year old 

affected sibling died at age 2. 

Genetic Disease 

Sickle Cell Anemia & Thalassemia 

EFS (44 patients)' After (Related) Cord Blood Tx 

(01::=\ ........... , ..... .... ....................................... > n events 

.~ 60 - -- Sickle cell disease 11 1 

CIl 

~ 

o 40 - -- Thalassemia 33 7 

20- P = 0.50 

o-~_-. __ -. __ -. __ .-__ ~ 

I I I I I 

o 500 1,000 1,500 2,000 2,500 

Days Post Transplant 

4 years Post 

Transplant for 

Thalassemia 

Both related and unrelated cord blood transplants can successfully treat 

children with hemoglobinopathies, correcting the defect. If the transplant 

Is performed early in life, survivals are ~80%. 

* Blood; November 17, 2002 
22 

Senator BROWNBACK. Is there legislation introduced to do that, 

on either the House or the Senate side? Do you know? 

Dr. KURTZBERG. There is one in progress, but it has not been introduced yet. 


612PABLO15.eps 612PABLO16.eps

Summary 

Demonstrated Treatments 

Hematologic malignancies 

- l eukemia, lymphoma 

Immunodeficiency diseases 

- SCID, CIO, CVID, WAS 

Bone marrow failure syndromes 

- Fanconi Anemia, Severe aplasti c anemia 

Hemoglobinopathies 

- Sickle Cell Anemia 

- Thalassemia Major 

Inborn errors of metabolism - ADL, MLD, GlO 

- MPS I, II, III, VI 

- r ay Sachs Disease 

Projected Benefits 

Routine treatm ent for 

thousands of patients 

with cancer and genetic 

diseases! year 

thousands 

Pa tienls 

Irl}atcd 

-""'!!"!"!r~~~~::::::=:=~--------'r----~ hundreds 

1988 

1" 

Patient 

1992 1996 

1" NIH • 1" FDA INO 

sponsored • NIH sponsored 

public e BB COBLT Study 

2003 

• 3,000 patients 

• FDA license 

under review 

(PROPOSAL) 

2008 

Inventory of 

150,000 ethnica lly 

diverse, high cell 

dose CB unit 

achieved 

2013 

To Establish a National Cord Blood Bank 

PURPOSE 

• To provide well-matched grafts with good cell 

doses for patients of all ethnic groups 

• To support cell therapy research with cord blood 

stem cells. 

METHOD 

• To create a network of 4-6 licensed U.S. cord 

blood banks that will build a public, high cell 

dose, ethnically balanced inventory of 150,000 

units over 5 years, with federal support. 
23 

Senator BROWNBACK. OK. 

Dr. KURTZBERG. There’s a draft of a bill. 

Senator BROWNBACK. All right. Because we’ll sure want to get 

that out and do that for you. This is very encouraging. And if you 

were one of the parents of one of those children, this is the hope 

you’ve been looking for. 

Dr. KURTZBERG. I’ve personally treated over 500 patients, and I 

have seen this work in children with otherwise fatal diagnoses. So 

it’s very important to be able to continue the work. 

Senator BROWNBACK. I’m sure that parents are absolutely ecstatic when they see that and see you. You’re—— 

Dr. KURTZBERG. Sometimes. 

Senator BROWNBACK.—an angel to them. 

Dr. McDonald, thank you very much for joining us and for being 

here today. 

STATEMENT OF JOHN W. MCDONALD, M.D., PH.D. 

DEPARTMENT OF NEUROLOGY, WASHINGTON UNIVERSITY 

SCHOOL OF MEDICINE 

Dr. MCDONALD. Good afternoon, Mr. Chairman. 

I’m Dr. John W. McDonald, and I’m an Assistant Professor at the 

Department of Neurology and Neurological Surgery and Director of 

the Spinal Cord Injury Program, at Washington University School 

of Medicine, in St. Louis. I’m also a staff physician at Barnes-Jewish Hospital, the Rehab Institute of St. Louis and St. Louis Children’s Hospital. 

I’m here today on behalf of the Coalition for the Advancement of 

Medical Research, a coalition of over 75 patient, scientific, and university organizations dedicated to ensuring that all forms of stem 

cell research be allowed to be explored here in the United States. 

The Coalition started 2 years ago to ensure that stem cell research receives the same sorts of funding that all other research receives from the Federal Government. The group also is dedicated 

to ensuring that critical cutting-edge research is not criminalized. 

As the Director of the Spinal Cord Injury Program, I see thousands of children and adults with devastating neurologic injuries, 

including spinal-cord injuries. These patients really have no practical alternatives for recovery of function after the injury has already occurred, such simple things as recovery of bowel and bladder control, or simply feeling a loved-one’s embrace. And only some 

of the 11,000 people who are injured every year recover any substantial function with traditional rehabilitation, which assumes 

that recovery is only possible after 6 months to 2 years. 

I’m currently working on a variety of ways to treat patients with 

spinal-cord injury or disease. And shown now is an example of a 

T2 weighted MRI image, the spinal cord is in the middle, if you 

see, down to the red box, it actually shows where the injury is. A 

really minute injury at this point in the nervous system becomes 

a really devastating problem. And I mentioned that there’s 11,000 

people injured each year. There’s a quarter of a million living with 

spinal-cord injury, and another four to five times that many with 

medical causes of spinal-cord injury, such as multiple sclerosis or 

ALS. 

24 

I’ve been working on a variety of ways to treat patients with spinal-cord injury and disease. For example, I’ve seen significant improvements in a very small group of patients, using activity-based 

therapy. This is a therapy that relies on providing pattern activations for someone who’s completely paralyzed, like putting a paralyzed person on a functional electrical stimulation bike, with this 

idea that the nervous system requires optimal activity in order for 

new cells to be born to optimize regeneration, now that we understand that the adult nervous system does have some limited capacity for regeneration. 

Shown here on this graph is the results of a patient that participated in this. Now, let me preface this by saying that this individual was completely paralyzed, from the neck down, from just 

below C–2 down, unable to breathe, move, or feel below that level, 

for the first 5 years. Traditional history would say that there’s no 

opportunity, absolutely, that this individual could regain any substantial function. And this individual began to recover substantial 

motor function, being able to move most of the joints in his body, 

to about 20 percent of normal on the scale. Of more importance 

was the recovery of sensation, which was about 70 percent of normal. Again, over the first 5 years, there was very limited recovery, 

and then a progressive recovery over the last 3 years, after institution of the activity-based recovery program, in the middle of 1999. 

We’ve done additional research now in animals that demonstrates that this type of activity actually mobilizes the stem cells 

that are present in the spinal cord below the level of the injury. 

What happens, below the level of the injury, in a chronic situation, 

is that the number of stem cells are reduced, unable to be there 

to be able to replace cells that are lost. And this activity appears 

to be repleting those cells so that they’re available, inasmuch as a 

stem cell transplant would allow. 

Senator BROWNBACK. By the physical stimulation that’s taking 

place. 

Dr. MCDONALD. Right. 

Now, while adult stem cells have potential for significantly improving clinical treatment of a wide range of diseases, I believe it’s 

critical that we also explore the use of embryonic stem cells. 

If you compare stem cells to a tree, adults stem cells have already developed and specialized down a particular path, or limb. 

On the other hand, embryonic stem cells are still at the base of the 

trunk, ready to be guided down any number of limbs. It’s, therefore, much more feasible to try to encourage embryonic stem cells 

to develop into whatever cell type is needed. 

As you can see from this video, this is an animal that’s treated, 

9 days after a spinal-cord injury, with embryonic stem cells that 

have been induced to become neuro progenitors. This is an animal 

that’s just a control; treated identically, except no cells. You can see 

it has great difficulty moving its hind limbs, raising his tail, and 

basically drags his behind. 

The next slide is a similar animal, but it’s been transplanted 

with embryonic stem cells, and you can see, really, a marked improvement in its ability to walk, stand on its hind limbs, and lift 

his tail. And the stage at which these cells were transplanted were 

neuro progenitors similar to those that can be derived from ESLs. 

25 

*The Coalition is comprised of nationally-recognized patient organizations, universities, scientific societies, foundations, and individuals with life-threatening illnesses and disorders, advocating for the advancement of breakthrough research and technologies in regenerative medicine—including stem cell research and somatic cell nuclear transfer—in order to cure disease 

and alleviate suffering. 

So, as you can see from the video, we have already found encouraging support for the use of embryonic stem cells to cure or treat 

some of the most debilitating diseases. The two rats that you have 

just seen have the same injury, but the rat that received the transplanted embryonic stem cells has recovered significantly more use 

of its hind limbs and tail. 

My hope is that one day the patients that I see in the Spinal 

Cord Injury Program will also be able to regain movement, just like 

that rat in this video. 

And as a scientist, I cannot guarantee that embryonic stem cells 

will lead to cures and treatments. I can tell you, however, that they 

hold great promise. Science is a process in which we knock on 20 

doors; 19 open, with nothing behind them; one opens to reveal a 

pot of gold. We can’t predict which door will be the magic door. 

The field of stem cell research, whether it be embryonic, adult, 

cord-blood stem cells, is extremely new. It’s entirely too early to 

rule out any one of these areas of research in favor of another. But 

my wheelchair-bound patients should not have to wait for us to explore each possibility one at a time. 

In the years that have been spent debating the issues here in 

Washington, research that could 1 day lead to cures and treatments for so many diseases has been held back. Some senior researchers have either left the United States to work elsewhere or 

have decided to work in other areas of biomedical research. And, 

more importantly, many of the next generation of researchers have 

decided to stay away from these areas because of the uncertain political environment. 

Mr. Chairman, please allow all forms of stem cell research to 

move forward—adult, cord blood, and embryonic—so that we can 

continue to look for medicine’s pot of gold. 

Thank you. 

[The prepared statement of Dr. McDonald follows:] 

PREPARED STATEMENT OF JOHN MCDONALD, M.D., PH.D. ON BEHALF OF THE

COALITION FOR THE ADVANCEMENT OF MEDICAL RESEARCH

Good afternoon Mr. Chairman and members of the Committee. I am Dr. John W. 

McDonald and I am an Assistant Professor in the Departments of Neurology, Neurological Surgery, Anatomy and Neurobiology and Director of the Spinal Cord Injury 

Program at Washington University School of Medicine in St. Louis. I am also a staff 

physician at Barnes-Jewish Hospital, the Rehabilitation Institute of St. Louis and 

St. Louis Children’s Hospital. 

I am here today on behalf of the Coalition for the Advancement of Medical Research,* a coalition of over 75 patient, scientific and university organizations dedicated to ensuring that all forms of stem cell research be allowed to be explored here 

in the United States. The Coalition started two years ago to ensure that stem cell 

research receives the same sorts of funding that all other research receives from the 

Federal government. The group also is dedicated to ensuring that critical, cuttingedge research is not criminalized. 

As the director of the Spinal Cord Injury Program, I see thousands of children 

and adults with devastating spinal cord injuries. These patients have no real hope 

for recovering functions most of us take for granted, from bowel and bladder control 

to simply feeling a loved one’s embrace. And only some of the 11,000 people who 

26 

get injured each year recover with traditional rehabilitation, which assumes that recovery is only possible after six months to 2 years. 

I am currently working on a variety of ways to treat patients with spinal cord 

injury or disease. For example, I’ve seen significant improvements in a very small 

group of patients using activity-based therapy, which relies on electrical stimulation 

to help patients exercise their paralyzed limbs. While significant, even those successes are minimal and extremely preliminary—it’s still unclear whether these techniques can help most spinal cord injuries, and to what extent they alone can restore 

function. We need to examine other promising approaches, and I believe that embryonic stem cells have the most potential. 

While adult stem cells also have potential for significantly improving clinical 

treatment of a wide range of diseases, I believe it is critical that we also explore 

the use of embryonic stem cells. If you compare stem cells to a tree, adult stem cells 

have already developed and specialized down a particular path, or limb. On the 

other hand, embryonic stem cells are still at the base of the trunk, ready to be guided down any of a number of limbs. It’s therefore much more feasible to try to encourage embryonic stem cells to develop into whichever type of cell is needed. 

As you can see from the video, we have already found encouraging support for 

the use of embryonic stem cells to cure or treat some of the most debilitating diseases. The two rats you see have the same injury, but the rat that received transplanted embryonic stem cells has recovered significantly more use of its hind legs 

and tail. 

My hope is that one day the patients I see in the Spinal Cord Injury Program 

will also be able to regain movement, just like the rat in this video. 

As a scientist, I cannot guarantee that embryonic stem cells will lead to cures and 

treatments. I can tell you, however, that they hold great promise. Science is a process in which we knock on 20 doors: Nineteen open with nothing behind them; One 

opens to reveal a pot of gold. We cannot predict which door will be that magic door. 

The field of stem cell research, whether it be embryonic, adult or cord blood stem 

cells, is still extremely new. It is entirely too early to rule out any one of these areas 

of research in favor of any other. My wheelchair bound patients should not have 

to wait for us to explore each possibility one at a time. 

In the years that have been spent debating the issue here in Washington, research that could one day lead to cures and treatments for so many diseases has 

been held back. Some senior researchers have either left the United States to work 

elsewhere or have decided to work in other areas of biomedical research. And many 

of the next generation of researchers has decided to stay away for these areas because of the uncertain political environment. Mr. Chairman, please allow all forms 

of stem cell research to move forward, adult, cord-blood and embryonic, so that we 

can continue to look for medicine’s pot of gold. 

Senator BROWNBACK. Thank you, Dr. McDonald. And thank you 

for your passion and your heart and your work to help others be 

able to walk. 

Dr. Peduzzi-Nelson, we have 12 minutes, I think, they’re just 

telling me, left in the vote. So I think we’ll try to get your testimony in before I head over to vote. 

But I’m delighted to have you here, and please proceed with your 

testimony. 

STATEMENT OF JEAN D. PEDUZZI-NELSON, PH.D. 

DEPARTMENT OF PHYSIOLOGICAL OPTICS 

UNIVERSITY OF ALABAMA AT BIRMINGHAM 

Dr. PEDUZZI-NELSON. What I’m going to show is that these 20 

doors are partially opened. We can see what doors contain the pots 

of gold and what doors contains gremlins that we need to close permanently. I agree with Dr. McDonald that we’re not knocking on 

these doors equally. Even with the Federal ban, the vast majority 

of studies are still using embryonic animal stem cells and human 

stem cell lines. The ban does not affect animal stem cell research. 

Using a person’s own stem cells is the area of research that’s being 

neglected. 

27 

I would like to quickly review the results of some clinical and 

pre-clinical trials that clearly shows where the pots of gold are and 

where the gremlins are. We’ve already heard some testimony that 

there’s definitely pots of gold for a number of children, using 

human umbilical cord blood, and also that the work that Dr. Hess 

presented, using bone marrow, and also Dr. McDonald’s work with 

rehabilitative therapy—are all very viable, wonderful areas to pursue. 

In terms of spinal-cord injury, I’d like to present the results of 

two clinical trials and show their results using an exact same test. 

In these trials, they were using tissue, neural tissue. And how this 

relates to the stem cell issue is, if you put this tissue—transplant 

it into the brain or spinal cord, the cells that survive are the stem 

cells, or the early derivatives of these stem cells. 

In a clinical trial that took place at the University of Florida that 

began in 1997, minced fetal spinal-cord tissue was used. The results of the first two patients have been published and are presented on the left side of the first three graphs. Their finding was 

that there was very little change in their condition. However, in 

another study that’s an ongoing trial in Portugal, person’s own olfactory mucosa was used. All of the patients in this study, as you 

can see in the first graph, in the light-touch ASIA scores, and in 

the next graph, using the pin-prick ASIA scores, and in the next 

graph, using the motor scores, that there was some improvement 

in actually all the patients that received the transplant by the first 

month after the transplant of their own olfactory mucosa. 

And furthermore, the first patient that was treated, after 15 

months after—16 months after the treatment, regained bladder 

control. And I don’t if many people in the audience know this, but 

this is a very severe problem with people with spinal-cord injury. 

And this woman no longer needs catheters at all. 

What’s interesting is, at the Portuguese studies, they had no rehabilitative methods available to them. There was no rehab therapy at all. The improvement was all what just happened naturally. 

And much greater improvement might have occurred if they had 

resources to have rehab therapy. 

I’d like to move on to—in the next graph, to the results of two 

Parkinson’s trials. These are clinical trials that clearly show some 

difference in the results. In a study by Freed and Associates done 

several years ago, human fetal stem cells were injected into the 

brain. And, on the left, you see the results of that study. There was 

a 28 percent improvement in the younger patients. ‘‘Younger,’’ in 

this study, which I like, means less than 60 years old. However, 

at about 1 year after the transplant, there was a very devastating 

result in 15 percent of the patients. They got significantly worse 

because of overgrowth of these embryonic cells that were placed in 

the brain, and they were much worse in function than they had 

been previously. 

However, there’s been another clinical trial in Parkinson’s, and 

this was using the person’s own stem cells from their brain. And 

this was a study done by Dr. Michel Levesque, in California. In 

this case, in this patient, there was an 83 percent improvement, 

and the patient had the treatment 2 years, and no detrimental side 

effects have been observed. 

28 

The experimental studies, animal studies, also provide indication 

of what is behind the doors. First, in the next slide, it’s true, maybe 

you can’t make a whole tree from adult neural stem cells, the cells 

that are from the brain. However, there’s lots of other stem cells 

in the body. So why would you even try to make every stem cell 

from an adult neural stem cell? 

Also, we know that you can make neurons, muscle cells, blood 

cells, from the stem cells in the adult brain. Also, you can get neurons or nerve cells or support cells to develop from bone, as Dr. 

Hess has mentioned, from skin, from blood, and my favorite, from 

fat stem cells. 

Second, the experimental studies that have been done using embryonic stem cells, as do the clinical trials, show that embryonic 

stem cells are dangerous, especially in terms of overgrowth. And 

studies by Bjourland and also by Dr. Gage and others have found 

tumor formation and sometimes blockage of the ventricular system 

can occur using embryonic stem cells. 

Third, my own work in rats with chronic severe spinal-cord injury show that adult stem cells can lead to a functional improvement. 

I think that it really gets down to a very basic question. If you 

or your loved one had a serious disease or injury, would you like 

them, or yourself, to receive your own stem cells or fetal, embryonic, or cloned stem cells? I think you don’t have to be a scientist 

to answer that question. But the answer to the question is also 

supported by the clinical trials and the pre-clinical animal trials 

that have been done so far. 

I would like to end by saying that the reason I’m here is that 

the victims of terrible diseases and injuries are again becoming victims to support a therapy that’s not in their best interest. With 

only a limited amount of funding available, more focus is needed 

in directing research in areas that can help people in the next five 

to 10 years, not several lifetimes away. 

Thank you. 

[The prepared statement of Dr. Peduzzi-Nelson follows:] 

PREPARED STATEMENT OF JEAN D. PEDUZZI-NELSON, PH.D., DEPARTMENT OF

PHYSIOLOGICAL OPTICS, UNIVERSITY OF ALABAMA AT BIRMINGHAM

‘‘THE Y IN THE ROAD’’ 

Thank you Senator Brownback and Senator McCain and distinguished senators 

of the subcommittee for the invitation to present to you today. Stem cells are a 

major medical breakthrough with tremendous potential but we are now at a ‘‘Y in 

the road’’ as far as the future of medicine. In deciding our course, the way is clouded 

by opposing ethical views, vested interests of certain scientists & the biotech community, political allegiances and celebrities. I would like the members of the subcommittee and the audience to set aside all those factors for just a few minutes. 

I ask you now to think about a very basic question: If your loved one was suffering 

from a terrible injury or disease, what type of stem cell treatment do you think would 

work the best: (1) their own cells or (2) cells derived from embryos, fetuses or cloned 

embryonic cells? I don’t think you need to be a scientist to answer that question. 

It also turns out that if you look at the scientific evidence, not speculation about 

the future by prominent scientists on either side of the issues, but just the facts of 

where we are today based on clinical and preclinical trials, the logical choice in medical treatment is also the best medical treatment. 

29 

1Wirth E.D. 3rd, Reier P.J., Fessler R.G., Thompson F.J., Uthman B., Behrman A., Beard J., 

Vierck C,J., Anderson D.K. Feasibility and safety of neural tissue transplantation in patients 

with syringomyelia.Journal of Neurotrauma. 18(9):911–29, 2001. 2http://www.diacrin.com/SCI%20Albany%20Surg.htm 

3Parks, D. Birmingham, News, Sunday, December 8, 2002, Olfactory nerves could help mend 

spinal injuries. http://www.scsnw.com/Nerves%20in%20nose%20may%20repair%20spinal%20 

cord%20injuries.htm 

I would now like to review the scientific data that prove that an intuitively obvious concept is also supported by the results of recent clinical trials and preclinical 

trials (experimental animal studies). First, I would like to review the clinical trials 

using stem cells and their derivatives in spinal cord injury and Parkinson’s disease. 

Two clinical trials using fetal tissue have been done in the U.S. and one on-going 

clinical trial in Portugal using a person’s own tissue. All of these spinal cord injury 

trials are important to the question of stem cell research because the cells that survive after the tissue transplant are the stem cells and their early derivatives. The 

mature cells in the tissue except for some support cells would die off. The first study 

using fetal tissue was done at the University of Florida, beginning in 1997, in the 

treatment of syringomelia—a condition in which a large cavity forms in the spinal 

cord. Minced spinal cords (SC) from 4–8 different human fetuses taken from elective 

abortions were grafted into the cavity in the spinal cord. At 18-month follow-up of 

the first 2 patients, the condition of the patients was not very different.1 Another 

study was performed more recently using pig fetal tissue at Washington University 

and SUNY/Albany. There have been no further announcements regarding this study 

although the first patient was done in April 2001.2 The study in Portugal has had 

impressive results using a person’s own olfactory mucosa.3 The olfactory mucosa 

lines the upper nasal cavity and contains stem cells and cells that encourage growth 

of nerve cell processes called olfactory ensheathing cells. Patients with severe (complete) spinal cord injuries were operated at 6 months following the injury. Other patients in this study (not reported below) were up to 7 years post-injury with similar 

or better results. On the next page are the charts comparing the results from the 

first 2 patients from each of the 2 different trials. In comparing the results of using 

embryonic tissues or using one’s own tissue: 

(1) There was little change in the condition of the patients using the embryonic 

tissue. There appeared to be no massive rejection even though 4–8 different 

embryos were used for each patient in the University of Florida trial and no 

reports of rejection in the trial using pig cells used in Washington University 

and SUNY/Albany. 

(2) In the Portuguese study, there were increases in motor and/or sensory scores 

by 1 month in almost all the patients receiving their own olfactory mucosa 

suggesting that a person’s own tissue is more effective. The first patient done 

regained bladder control at 16 months after the treatment and no longer uses 


612PEDUZ1.eps
30 

catheters. The second patient that had less improvement was the patient that 

had the largest lesion (6 cm) of all of the patients done so far. 

The changes observed might have been greater for the patients treated in Portugal if rehabilitative therapy was available there. 


612PEDUZ2.eps 612PEDUZ3.eps

70 

60 

50 

40 

30 

20 

10 

Total Light Touch ASIA Scores 

[] before 

[] 6 monthd after 

• 15 months after 

o ~"'---L...-

Aborted Fetal SC Person's Olfactory Mucosa 

Total Pin Prick ASIA Scores 

70 

60 

50 

40 

30 

20 

10 

o before 

o 6 month After 

• 15 months after 

o +---J"'---L...-

Aborted Fetal SC Person's Olfactory Mucosa 
31 

4Freed C.R., Greene P.E., Breeze R.E., Tsai W.Y., DuMouchel W., Kao R., Dillon S., Winfield 

H., Culver S., Trojanowski J.Q., Eidelberg D., Fahn S. (2001) Transplantation of embryonic 

dopamine neurons for severe Parkinson’s disease. New Engl. J. Med.. 344:710–9. 5Levesque, M.F. and T. Neuman Autologous transplantation of adult human neural stem cells 

and differentiated dopaminergic neurons for Parkinson’s disease: one year post-operative clinical 

and functional metabolic results. AANS31, 2002. 

The clinical trials in Parkinson’s disease had dramatic differences in their findings depending on the original source of the cells: fetuses or the person’s own cells. 

In both cases, the cells were matured in culture before being transplanted into the 

patient. A clinical trial was done by Dr. Freed and colleagues in which 19 patients 

received cells derived from 4 different fetuses with abortions at 7–8 weeks after conception.4 The patients that were under 60 years showed about a 28 percent improvement in the Unified Parkinson’s Disease Rating Scale (UPDRS). About 15 percent 

of these patients showed severe decline in function at 1 year after treatment. In another Parkinson’s study done by Dr. Michel Levesque, the patient who was 57 years 

old at the time of treatment, received cells derived from his own brain stem cells.5

This patient showed an 83 percent improvement in the UPDRS. Below is a chart 

that summarizes the percentage improvement in the 2 clinical trials. 

The greater improvement and lack of harmful late effects using a person’s own 

cells is primarily due to the fact that the cells were derived from an adult as opposed to fetuses. Of lesser contribution to the overall improvement probably was 

that the cells were genetically identical and not rejected. There was no evidence of 


612PEDUZ4.eps 612PEDUZ5.eps
32 

6 van Praag H. Schinder A.F. Christie B.R. Toni N. Palmer T.D. Gage F.H. Functional 

neurogenesis in the adult hippocampus. Nature. 415(6875):1030–4, 2002. 7 Janson C.G., T.M. Ramesh, M.J. During, P. Leone and J. Heywood 2001 Human intrathecal 

transplantation of peripheral blood stem cells in amyotrophic lateral sclerosis. J Hematotherapy 

& Stem Cell Res 10:93–915. 8 Bjorklund L.M.. Sanchez-Pernaute R.. Chung S.. Andersson T.. Chen I.Y.. McNaught K.S.. 

Brownell A.L.. Jenkins B.G.. Wahlestedt C.. Kim K.S.. Isacson O. Embryonic stem cells develop 

into functional dopaminergic neurons after transplantation in a Parkinson rat model. [comment]. [Journal Article] Proceedings of the National Academy of Sciences of the United States 

of America. 99(4):2344–9, 2002. 9 Reynolds B.A., Wiess S. 1992. Generation of neurons and astrocytes from isolated cells of 

the adult mammalian central nervous system. Science 255:1701–1710. 10 Richards, Lric T.J., Bartlett P.F. 1992. De nonv generation of neuronal cells from the adult 

mouse brain. Proc. Natl Acad Sci USA 89:8591–8595. 11 Eriksson P.S., Perfilieva E., Bjork-Eriksson, T., Alborn A.M., Nordborg C., Peterson D.A., 

Gage F.H. 1998. Neurogenesis in the adult human hippocampus. Nat Med. 4:13113–1317. 12Gritti A., Vescovi A.L., Galli R. Adult neural stem cells: plasticity and developmental potential. Journal of Physiology-Paris. 96(1–2):81–90, 2002. 

massive rejection in any of the studies using fetal cells/tissues, even when pig cells 

were used without long-term immune-suppressing drugs to prevent rejection. However, better results were obtained using person’s own adult cells. The study by 

Freed and colleagues also suggests that the primary problem with the fetal cells is 

not rejection. Using cells derived from fetuses, the severe functional deterioration 

seen in several patients was due to overgrowth of the cells derived from fetuses, not 

a lack of cell survival. 

It is rather ironical that the qualities cited for the superiority of embryonic or 

fetal stem cells are actually responsible for causing problems. Rapid growth is not 

always a desirable quality as clearly seen with weeds in a garden or cancer in the 

body. In the Parkinson’s study, cells derived from the embryo and the adult were 

both allowed to mature in culture, but the end result was quite different. As the 

graph demonstrates, the patient’s own cells markedly improved and no debilitating 

side effects were observed. A possible explanation for these findings is that adult 

stem cells are the natural components of the adult body and endogenous mechanisms exist to control their growth and maturation to replace damaged neurons.6

The cells from the adult may have certain molecules on their surface (ligands or receptors) that keeps the cells from uncontrolled growth. Both studies allowed the 

stem cell to mature before implantation. If maturation of stem cell is a necessary 

safety step, then the fact that embryonic cells are so immature is a disadvantage. 

It would be possible and simpler to have large-scale commercialization of cells derived from embryos or fetuses but the end product would be grossly inferior for the 

recipients. There are many types of adult human stem cells that are readily available that lack the problems of overgrowth, rejection, and disease transmission. Most 

people do not need a total body replacement. Even if costly and complicated procedures of cloning are done to produce the human stem cells (not technically possible 

yet), the cells will not be genetically identical because of the mitochondrial DNA and 

improper imprinting. There is evidence that the debate is raging in the scientific 

community. A recent scientific article describing a clinical trial included an opinion 

that the authors, although using a patient’s own blood stem cells, in no way support 

a ban on using human embryonic stem cells.7

Preclinical Trials: Preclinical trials (experimental animal studies) not only provide 

the basis for future clinical trials described above, but also support the same conclusion that is reached in reviewing the clinical trials. There is abundant evidence that 

adult stem cells can be used as a therapy and are readily available in people. The 

conclusion from the preclinical studies is that adult stem cells work just as well, 

if not better, than embryonic stem cells and are probably safer.8 There is no need 

for embryonic stem cells especially cloned ones. 

Ten years ago, it was discovered that stem cells exist in the adult brain and spinal cord and can be readily isolated.9 10 Many initial ideas about adult stem cells 

in the brain were wrong. For example, the cells were first thought to only be present 

in rodents, but later found in people.11 It was once thought that only embryonic 

stem cells have the capacity to become many different cell types. More recently, it 

has been found that neural stem cells from adults have this potential.12 Stem cells 

and their cellular derivatives may be useful in many ways. In the nervous system, 

they can be replacement neurons, source of growth factors, or a substrate of growth. 

Another misconception was that adult stem cells might not be functional in their 

ability to transmit a signal to another neuron. There is recent evidence that adult 

stem cells can mature and form functional connections with other neurons in culVerDate Nov 24 2008 06:41 May 20, 2013 Jkt 075679 PO 00000 Frm 00036 Fmt 6633 Sfmt 6621 S:\GPO\DOCS\80903.TXT JACKIE
33 

13Toda H., Takahashi J., Mizoguchi A., Koyano K., Hashimoto N., Neurons generated from 

adult rat hippocampal stem cells form functional glutamatergic and GABAergic synapses in 

vitro. Experimental Neurology. 165(1):66–76, 2000. 14Song, H-j, C.F. Stevens, F.H. Gage, Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons. Nature Neuroscience5: 438–445, 2002. 15Suslov O.N., Kukekov V.G., Ignatova T.N., Steindler D.A. Neural stem cell heterogeneity 

demonstrated by molecular phenotyping of clonal neurospheres. Proceedings of the National 

Academy of Sciences of the United States of America. 99(22):14506–11, 2002. 16 Akiyama Y., Honmou O., Kato T., Uede T., Hashi K., Kocsis J.D. Transplantation of clonal 

neural precursor cells derived from adult human brain establishes functional peripheral myelin 

in the rat spinal cord. Experimental Neurology. 167(1):27–39, 2001. 17Murrell W., Bushell G.R., Livesey J., McGrath J., MacDonald K.P., Bates P.R., Mackay-Sim 

A. Neurogenesis in adult human. NeuroReport. 7(6):1189–94, 1996. 18Feron F.. Perry C., McGrath J.J., Mackay-Sim A. New techniques for biopsy and culture 

of human olfactory epithelial neurons. Archives of Otolaryngology—Head & Neck Surgery. 

124(8):861–6, 1998. 19Seigel G.M., Sun W., Salvi R., Campbell L.M., Sullivan S., Reidy J.J. Human corneal stem 

cells display functional neuronal properties. Molecular Vision. 9:159–63, 2003. 20 Arsenijevic Y., Taverney N., Kostic C., Tekaya M., Riva F., Zografos L., Schorderet D., 

Munier F. Non-neural regions of the adult human eye: a potential source of neurons?. Investigative Ophthalmology & Visual Science. 44(2):799–807, 2003. 21Miura M., Gronthos S., Zhao M., Lu B., Fisher L.W., Robey P.G., Shi S. SHED: Stem cells 

from human exfoliated deciduous teeth. Proceedings of the National Academy of Sciences of the 

United States of America. 100(10):5807–12, 2003. 22Deng W., Obrocka M., Fischer I., Prockop D.J. In vitro differentiation of human marrow 

stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic 

AMP. Biochemical & Biophysical Research Communications. 282(1):148–52, 2001. 23 Hung S.C., Cheng H., Pan C.Y., Tsai M.J., Kao L.S., Ma H.L. In vitro differentiation of sizesieved stem cells into electrically active neural cells. Stem Cells. 20(6):522–9, 2002. 24Toma J.G., Akhavan M., Fernandes K.J., Barnabe-Heider F., Sadikot A., Kaplan D.R., Miller F.D. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nature 

Cell Biology. 3(9):778–84, 2001. 25Mezey E., Key S., Vogelsang G., Szalayova I., Lange G.D., Crain B.Transplanted bone marrow generates new neurons in human brains. Proceedings of the National Academy of Sciences 

of the United States of America. 100(3):1364–9, 2003. 26Shihabuddin L.S., Horner P.J., Ray J., Gage F.H. Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. Journal of Neuroscience. 20(23):8727–35, 

2000. 27 Akiyama Y., Honmou O., Kato T., Uede T., Hashi K., Kocsis J.D.: Transplantation of clonal 

neural precursor cells derived from adult human brain establishes functional peripheral myelin 

in the rat spinal cord. Exp Neurol 167:27–39, 2001. 28 Hou L.L., Zheng M., Wang D.M., Yuan H.F., Li H.M., Chen L., Bai C.X., Zhang Y., Pei 

X.T.[Migration and differentiation of human bone marrow mesenchymal stem cells in the rat 

brain].Sheng Li Hsueh Pao—Acta Physiologica Sinica. 55(2):153–9, 2003. 29Liker M.A., Petzinger G.M., Nixon K., McNeill T., Jakowec M.W. Human neural stem cell 

transplantation in the MPTP-lesioned mouse. Brain Research. 971(2):168–77, 2003. 30Palmer T.D., Schwartz P.H., Taupin P., Kaspar B., Stein S.A., Gage F.H. Cell culture. Progenitor cells from human brain after death. Nature. 411(6833):42–3, 2001. 

ture.13 14 A surprising finding was that many cells in the adult (not just the cells 

in the brain and spinal cord) have the potential to be neurons. Sources of adult 

human stem cells that are capable of forming neurons include the brain,15 16 olfactory mucosa in the upper nose,17 18 cornea,19 choroid and sclera 20 of the eye, 

teeth,21 bone marrow.22 23 and skin.24 Further evidence that bone marrow can be 

a source of neurons for the brain is supported by findings in the patients’ brains 

who have received bone marrow transplants.25 There is no reason to use embryonic/ 

fetal tissue or to clone people to obtain genetically similar embryonic stem cells 

when there is a ready supply of stem cells in adult humans. 

There are several studies that support the usefulness of adult stem cells. Stem 

cells obtained from adult spinal cord have been shown to survive and mature into 

neurons when transplanted into the brain.26 Transplantation of stem cells from 

adult human brain causes myelination to occur in a focally demyelinated spinal cord 

of the rat.27 Demyelination is common in spinal cord injury and disease states such 

as Multiple Sclerosis, and interferes with signal conduction between the neurons. 

Human cells from adult have been used to treat animal models of disease states . 

For example, human cells led to functional improvement in animal models of Parkinson’s disease using human bone cells 28 or using neural stem cells.29 Human 

brain adult stem cells can even be obtained after death 30 so if a person’s own stem 

cells are not used; there are other less objectionable alternatives. Another alternative to the use of embryonic stem cells is human umbilical cord blood. Human 

34 

31Sanchez-Ramos J.R., Song S., Kamath S.G., Zigova T., Willing A., Cardozo-Pelaez F., 

Stedeford T., Chopp M., Sanberg P.R. Expression of neural markers in human umbilical cord 

blood. Experimental Neurology. 171(1):109–15, 2001. 32 BuzaAska L., Stachowiak E., Stachowiak M., DomaAska-Janik K. Neural stem cell line derived from human umbilical cord blood—morphological and functional properties.Journal of 

Neurochemistry. 85 Suppl 2:33, 2003. 33Goodwin H.S., Bicknese A.R., Chien S.N., Bogucki B.D., Quinn C.O., Wall D.A. Multilineage 

differentiation activity by cells isolated from umbilical cord blood: expression of bone, fat, and 

neural markers. Biology of Blood & Marrow Transplantation. 7(11):581–8, 2001. 34Lu D., Sanberg P.R., Mahmood A., Li Y., Wang L., Sanchez-Ramos J., Chopp M. Intravenous administration of human umbilical cord blood reduces neurological deficit in the rat after 

traumatic brain injury.Cell Transplantation. 11(3):275–81, 2002. 35Sanberg P.R., Chopp M., Willing A.E., Zigova T., Saporta S., Song S., Bickford P., 

Garbuzova-Davis S., Newman M., Cameron D.F., Sanchez-Ramos J. Potential of umbilical cord 

blood cells for brain repair.Journal of Neurochemistry. 81 Suppl 1:83, 2002. 36Shen J.S., Watabe K., Ohashi T., Eto Y. Intraventricular administration of recombinant 

adenovirus to neonatal twitcher mouse leads to clinicopathological improvements. Gene Therapy. 8(14):1081–7, 2001. 37Schwarz E.J., Reger R.L., Alexander G.M., Class R., Azizi S.A., Prockop D.J. Rat marrow 

stromal cells rapidly transduced with a self-inactivating retrovirus synthesize L–DOPA in vitro. 

Gene Therapy. 8(16):1214–23, 2001. 38 Nakano K., Migita M., Mochizuki H., Shimada T. Differentiation of transplanted bone marrow cells in the adult mouse brain. Transplantation. 71(12):1735–40, 2001. 39Park K.W., Eglitis M.A., Mouradian M.M. Protection of nigral neurons by GDNF-engineered 

marrow cell transplantation. Neuroscience Research. 40(4):315–23, 2001. 40 Ehtesham M., Kabos P., Gutierrez M.A., Chung N.H., Griffith T.S., Black K.L., Yu J.S. Induction of glioblastoma apoptosis using neural stem cell-mediated delivery of tumor necrosis factor-related apoptosis-inducing ligand. Cancer Research. 62(24):7170–4, 2002l. 41 Hofstetter C.P., Schwarz E.J., Hess D., Widenfalk J., El Manira A., Prockop D.J., Olson L. 

Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proceedings of the National Academy of Sciences of the United States of America. 99(4):2199–204, 

2002. 42 Akiyama Y., Radtke C., Honmou O., Kocsis J.D. Remyelination of the spinal cord following 

intravenous delivery of bone marrow cells. [Journal Article] GLIA. 39(3):229–36, 2002. 43Lu D., Mahmood A., Wang L., Li Y., Lu M., Chopp M. (2001) Adult bone marrow stromal 

cells administered intravenously to rats after traumatic brain injury migrate into brain and improve neurological outcome. Neuroreport 12:559–63. 44 Rideout W.M. III, Hochedlinger K., Kyba, M. Daley Q., and Jaenisch R. Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy Cell 109:17–27 45Kato T., Honmou O., Uede T., Hashi K., Kocsis J.D. Transplantation of human olfactory 

ensheathing cells elicits remyelination of demyelinated rat spinal cord. GLIA. 30(3):209–18, 

2000. 46 VerdA E., GarcA-a-AlA-as G., ForA(C)s J., LA pez-Vales R., Navarro X. Olfactory 

ensheathing cells transplanted in lesioned spinal cord prevent loss of spinal cord parenchyma 

and promote functional recovery GLIA. 42(3):275–86, 2003. 

umbilical cord blood has the potential to form neurons,31 32 as well as other cell 

types.33 Human umbilical cord blood injected IV caused a functional improvement 

when injected into experimental animals with traumatic brain injury or stroke.34 35

In the case of genetic defects, there are several other alternatives to cloning. One 

is gene therapy that has been successfully used in mice 36 and humans. More recently stem cells have been used as vehicle to deliver genes to the brain.37 38 39 40. Bone marrow stromal cells from adult rats promote functional recovery after spinal 

cord injury in rats when given 1 week after injury,41 even when the cells are injected intravenously.42 Bone marrow stromal cells also will migrate to site of a head 

injury when given IV and caused a functional improvement.43

Below is a brief summary (in italics) of recent findings using other treatments besides stem cell for injuries and diseases of the nervous system. This summary is 

meant to make 2 major points: 

(1) Other treatments used alone or in combination with adult stem cells may hold 

the greatest promise in treating spinal cord injury and other damage to the 

nervous system. 

(2) While there is no ban on animal cloning, a review of recent literature revealed 

more than 40 articles of promising treatments other than stem cells for spinal 

cord injury but only 1 or just a few articles showing any therapeutic benefit 

of therapeutic cloning. The one article that received significant press coverage 

attempted to show a benefit of cloning in an animal study also revealed some 

of the difficulties with this procedure.44

Other cell types: Other cell types that do not form neurons also help in recovery. 

After selective demyelination in rat spinal cord, olfactory ensheathing cells 

myelinated axons 45 and led to greater motor and somatosensory evoked potentials 

and a better functional outcome.46 Olfactory ensheathing cells promote locomotor reVerDate Nov 24 2008 06:41 May 20, 2013 Jkt 075679 PO 00000 Frm 00038 Fmt 6633 Sfmt 6621 S:\GPO\DOCS\80903.TXT JACKIE
35 

47Lu J., Feron F., Mackay-Sim A., Waite P.M. Olfactory ensheathing cells promote locomotor 

recovery after delayed transplantation into transected spinal cord. Brain 125:14–21, 2002. 48 Ramon-Cueto A., Cordero M.I., Santos-Benito F.F., Avila J. Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron 2000 Feb;25(2):425–35. 49 Nash H.H., Borke R.C., Anders J.J. Ensheathing cells and methylprednisolone promote 

axonal regeneration and functional recovery in the lesioned adult rat spinal cord. Journal of 

Neuroscience. 22(16):7111–20, 2002. 50 Novikova L., Novikov L., Kellerth J.O. Brain-derived neurotrophic factor reduces necrotic 

zone and supports neuronal survival after spinal cord hemisection in adult rats. Neuroscience 

Letters. 220(3):203–6, 1996. 51Koda M., Murakami M., Ino H., Yoshinaga K., Ikeda O., Hashimoto M., Yamazaki M., 

Nakayama C., Moriya H. Brain-derived neurotrophic factor suppresses delayed apoptosis of 

oligodendrocytes after spinal cord injury in rats. Journal of Neurotrauma. 19(6):777–85, 2002. 52Schnell, L., R. Schneider, R. Kolbeck, Y.A. Bard and M.E. Schwab (1994) Neurotrophin-3 

enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. 

Nature 367:170–173. 53Tuszynski M.H., Grill R., Jones L.L., Brant A., Blesch A., L.A. w K., Lacroix S., Lu P. NT– 

3 gene delivery elicits growth of chronically injured corticospinal axons and modestly improves 

functional deficits after chronic scar resection. Experimental Neurology. 181(1):47–56, 2003. 54Liu W.G., Luo Y.X. The early protective effects of basic fibroblast growth factor on acute 

spinal cord injury in rats. [Chinese]Chung-Kuo Hsiu Fu Chung Chien Wai Ko Tsa Chih/Chinese 

Journal of Reparative & Reconstructive Surgery. 13(5):291–4, 1999. 55Lee Y.S., Baratta J., Yu J., Lin V.W., Robertson R.T. AFGF promotes axonal growth in rat 

spinal cord organotypic slice co-cultures. Journal of Neurotrauma. 19(3):357–67, 2002. 56Lee Y.S., Hsiao I., Lin V.W. Peripheral nerve grafts and aFGF restore partial hindlimb 

function in adult paraplegic rats. Journal of Neurotrauma. 19(10):1203–16, 2002. 57 Brooker G.J., Kalloniatis M., Russo V.C., Murphy M., Werther G.A., Bartlett P.F. Endogenous IGF–1 regulates the neuronal differentiation of adult stem cells. J. Neurosci. Res. 

59(3):332–41, 2000. 58O’Kusky J.R., Ye P., D’Ercole A.J. Insulin-like growth factor-I promotes neurogenesis and 

synaptogenesis in the hippocampal dentate gyrus during postnatal development. Journal of Neuroscience. 20(22):8435–42, 2000. 

covery in the transected cord after delayed transplantation.47 These cells were also 

found to stimulate growth of motor axons.48 Olfactory ensheathing cells when used 

with methylprednisolone promoted functional recovery and axonal regeneration 

after lesioning of the corticospinal tract.49

Growth Factors: With the discovery of new growth factors such as neurotrophic 

factors and cytokines that influence the survival and growth of neurons, it was 

hoped that spinal cord injury could soon be treated. Brain-derived neurotrophic factor (BDNF) reduces the necrotic zone and supports neuronal survival after spinal 

cord hemisection in adult rats 50 and suppresses apoptosis of oligodendrocytes.51

Also neurotrophin-3 (NT–3) enhances sprouting of corticospinal tract after adult spinal cord lesion 52 even in chronic SCI.53 Basic fibroblast growth factor (bFGF) reduced the pathology observed in spinal cord injured rats receiving bFGF via the 

CSF following a spinal cord injury.54 Acidic fibroblast growth factor (aFGF) promote 

axonal growth between spinal cord slices 55 and when combined with peripheral 

nerve segments led to improved locomotor function after spinal transection.56 Insulin growth factor 1 (IGF–1) stimulates myelin formation in the nervous system 57

and also stimulates the production of neurons and synapse formation.58 In our own 

lab studies using cells derived from adult stem cells to treat rats with severe, chronic spinal cord injuries, significant functional improvement was observed when the 

factors (diff media) used for stem cells maturation are used alone. Further improvements are found when adult stem cell (SC) or IGF–1 is added to the treatment suggesting the benefit of combination treatments. 

36 

59Tyor W.R., Avgeropoulos N., Ohlandt G., Hogan E.L. Treatment of spinal cord impact injury 

in the rat with transforming growth factor-beta. Journal of the Neurological Sciences. 200(1– 

2):33–41, 2002. 60 Iwakawa M., Mizoi K., Tessler A., Itoh Y. Intraspinal implants of fibrin glue containing glial 

cell line-derived neurotrophic factor promote dorsal root regeneration into spinal cord. 

Neurorehabilitation & Neural Repair. 15(3):173–82, 2001. 61 Benowitz L.I., D.E. Goldberg, J.R. Madsen, D. Soni and N. Irwin Inosine stimulates extensive axon collateral growth in the rat corticospinal tract after injury. PNAS 96: 13486–13490, 

1999. 62Kojima A., Tator C.H. Intrathecal administration of epidermal growth factor and fibroblast 

growth factor 2 promotes ependymal proliferation and functional recovery after spinal cord injury in adult rats. Journal of Neurotrauma. 19(2):223–38, 2002. 63 Bilak M.M., Kuncl R.W. Delayed application of IGF–I and GDNF can rescue already injured 

postnatal motor neurons. Neuroreport. 12(11):2531–5, 2001. 64Liebl D.J., Huang W., Young W., Parada L.F. Regulation of Trk receptors following contusion of the rat spinal cord.Experimental Neurology. 167(1):15–26, 2001. 65 Jin Y., Tessler A., Fischer I., Houle J.D. Fibroblasts genetically modified to produce BDNF 

support regrowth of chronically injured serotonergic axons.Neurorehabilitation & Neural Repair. 

14(4):311–7, 2000. 66Grill R.J., A. Blesch and M.H. Tuszynski (1997). Robust growth of chronically injured spinal 

cord axons induced by grafts of genetically modified NGF-secreting cells. Exper. Neurol. 148:44– 

452. 67Lu K.W., Chen Z.Y., Jin D.D., Hou T.S., Cao L., Fu Q. Cationic liposome-mediated GDNF 

gene transfer after spinal cord injury. Journal of Neurotrauma. 19(9):1081–90, 2002. 

Another cytokine, transforming growth factor-beta (TGF-beta) caused a decrease 

in the lesion size following SCI.59 Yet another cytokine, glial cell line-derived 

neurotrophic factor (GDNF) when incorporated in a fibrin glue promotes dorsal root 

regeneration into spinal cord.60 Metabolites such as inosine also appear to encourage growth of spared axons and possibly injured axons following spinal cord injury.61 The spinal cord distal to the injury consists of cells that are shrunken and 

appear unhealthy. One possibility is that this natural metabolite especially when 

used as part of a combination treatment may stimulate the growth of these cells. 

Many recent studies have used a combination of growth factors. The combination 

of EGF and bFGF showed better functional recovery than vehicle or either factor 

alone.62 Insulin-like growth factor (IGF) and epidermal growth factor (EGF) rescued 

motor neurons better than each individually even when delivered after 4-week 

delay.63 Although significant stimulation of axonal growth is observed with growth 

factors, problems in delivery, penetration, and down-regulation or truncation of receptors 64 have perhaps kept their full potential from being realized. 

Gene therapies: To overcome the problem of the growth factors actually reaching 

the affected neurons, two strategies have been taken. First, certain cell types have 

been modified to produce growth factors then grafted into the injury site. Second, 

endogenous cells have been genetically modified primarily using virus vectors. 

Fibroblasts genetically modified to produce BDNF65 or NGF66 support regrowth of 

chronically injured axons. The in vivo transfer of GDNF cDNA can promote axonal 

regeneration and enhance locomotion functional recovery.67 Neurotrophin-secreting 

Schwann cell implants improved urinary bladder structure after spinal cord contuVerDate Nov 24 2008 06:41 May 20, 2013 Jkt 075679 PO 00000 Frm 00040 Fmt 6633 Sfmt 6621 S:\GPO\DOCS\80903.TXT JACKIE

612PEDUZ6.eps
37 

68Sakamoto K., Uvelius B., Khan T., Damaser M.S. Preliminary study of a genetically engineered spinal cord implant on urinary bladder after experimental spinal cord injury in rats. 

Journal of Rehabilitation Research & Development. 39(3):347–57, 2002. 69Zhou L., Baumgartner B.J., Hill-Felberg S.J., McGowen L.R., Shine H.D. Neurotrophin-3 expressed in situ induces axonal plasticity in the adult injured spinal cord.Journal of Neuroscience. 23(4):1424–31, 2003. 70Miura T., Tanaka S., Seichi A., Arai M., Goto T., Katagiri H., Asano T., Oda H., Nakamura 

K. Partial functional recovery of paraplegic rat by adenovirus-mediated gene delivery of constitutively active MEK1.Experimental Neurology. 166(1):115–26, 2000. 71 Jackson, C.A., C. Cobbs, J.D. Peduzzi, M. Novak and C.D. Morrow (2001) Repetitive 

Intrathecal injections of Poliovirus Replicons result in gene expression in neurons of the central 

nervous system without pathogenesis. Human Gene Therapy, 12:1827–1842. 72 Holmes T.C., de Lacalle S., Su X., Liu G., Rich A., Zhang S. (2000) Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds. PNAS 97:6728–33. 73Liu S., Said G., Tadie M. Regrowth of the rostral spinal axons into the caudal ventral roots 

through a collagen tube implanted into hemisected adult rat spinal cord. Neurosurg. 49:143– 

50, 2001. 74 Houle J.D. and M.K. Ziegler (1994) Bridging a complete transection lesion of adult rat spinal cord with growth factor-treated nitrocellulose implants. J. Neural Transplant. & Plast. 

5:1115–124. 75 Novikov L.N., Novikova L.N., Mosahebi A., Wiberg M., Terenghi G., Kellerth J.O. A novel 

biodegradable implant for neuronal rescue and regeneration after spinal cord injury. Biomaterials. 23(16):3369–76, 2002. 76Teng Y.D., Lavik E.B., Qu X.. Park K.I., Ourednik J., Zurakowski D., Langer R., Snyder 

E.Y. Functional recovery following traumatic spinal cord injury mediated by a unique polymer 

scaffold seeded with neural stem cells. Proceedings of the National Academy of Sciences of the 

United States of America. 99(5):3024–9, 20. 77Woerly S., Doan V.D., Evans-Martin F., Paramore C.G., Peduzzi J.D. Spinal cord reconstruction using NeuroGel implants and functional recovery after chronic injury.Journal of Neuroscience Research. 66(6):1187–97, 2001. 78 Hauben E., Agranov E., Gothilf A., Nevo U., Cohen A., Smirnov I., Steinman L., Schwartz 

M. Posttraumatic therapeutic vaccination with modified myelin self-antigen prevents complete 

paralysis while avoiding autoimmune disease. Journal of Clinical Investigation. 108(4):591–9, 

2001. 79http://www.biospace.com/companylprofile.cfm?CompanyID=4350 80Popovich P.G., Guan Z., McGaughy V., Fisher L., Hickey W.F., Basso D.M. The 

neuropathological and behavioral consequences of intraspinal microglial/macrophage activation. 

Journal of Neuropathology & Experimental Neurology. 61(7): 623–33, 2002. 

sion.68 NT–3 gene in an adenoviral vector was delivered to the spinal motoneurons 

by retrograde transport through the sciatic nerve, causing induced growth of axons 

from the intact corticospinal tract across the midline to the denervated side.69 Another approach is to actually stimulate one of the intracellular pathways that play 

a role in neurite outgrowth. Viral delivery of vectors carrying the mutated form of 

MEK1 that activates of the extracellular-signal-regulated kinases (ERKs) induces 

axonal regeneration across the transection site of the spinal cord in young rats.70

Newer approaches that direct transient production of growth factors specifically in 

motor neurons also hold great promise.71

Substrate or Matrix: There have been several studies that provide a substrate for 

growth is useful. Self-assembling peptide scaffolds support differentiation as well as 

extensive neurite outgrowth in culture.72 When a collagen tube is implanted into 

hemisected adult rat spinal cord, there is growth of the rostral spinal axons into 

the caudal ventral roots.73 Growth factor-treated nitrocellulose implants that bridge 

a complete transection lesion of adult rat spinal cord caused regrowth of ascending 

sensory axons across the traumatic spinal cord injury site.74 Implants using polybeta-hydroxybutyrate (PHB) as carrier scaffold and containing alginate hydrogel, 

fibronectin, and Schwann cells can support neuronal survival and regeneration after 

spinal cord injury.75 Using a polymer scaffold seeded with stem cells led to better 

functional recovery in hemisected SC and appeared to encourage the growth of 

corticospinal axons.76 When a hydrogel is implanted into the injury site of a rat with 

chronic, severe SCI, there was improved function and evidence of blood vessels, and 

axonal growth.77

Modifying the Immune System: The immune system plays an important role in 

spinal cord injury. Many cytokines and other factors released by immune cells also 

influence neural cells. Several studies suggest a benefit of activated macrophages 

or specific T cells in reducing the amount of secondary injury and stimulating 

growth after spinal cord injury in rats.78 Recent clinical trials using activated 

macrophages are being conducted in Israel.79 However, others have found that activation of macrophages in a normal cord can actually cause axonal injury and 

demyelination 80 and suggests inherent danger of activating the immune system 

38 

81 Jones T.B., Basso D.M., Sodhi A., Pan J.Z., Hart R.P., MacCallum R.C., Lee S., Whitacre 

C.C., Popovich P.G. Pathological CNS autoimmune disease triggered by traumatic spinal cord 

injury: implications for autoimmune vaccine therapy. Journal of Neuroscience. 22(7):2690–700, 

2002. 82 Bethea J.R., Nagashima H., Acosta M.C., Briceno C., Gomez F., Marcillo A.E., Loor K., 

Green J., Dietrich W.D. Systemically administered interleukin-10 reduces tumor necrosis factoralpha production and significantly improves functional recovery following traumatic spinal cord 

injury in rats. [Journal Article] Journal of Neurotrauma. 16(10):851–63, 1999. 83Takami T., Oudega M., Bethea J.R., Wood P.M., Kleitman N., Bunge M.B. 

Methylprednisolone and interleukin-10 reduce gray matter damage in the contused Fischer rat 

thoracic spinal cord but do not improve functional outcome. Journal of Neurotrauma. 19(5):653– 

66, 2002. 84Merkler D., Metz G.A., Raineteau O., Dietz V., Schwab M.E. Fouad K.Locomotor recovery 

in spinal cord-injured rats treated with an antibody neutralizing the myelin-associated neurite 

growth inhibitor Nogo-A.Journal of Neuroscience. 21(10):3665–73, 2001. 85GrandPre T., Li S., Strittmatter S.M. Nogo-66 receptor antagonist peptide promotes axonal 

regeneration. Nature. 417(6888): 547–51, 2002. 86 Hermanns S., Klapka N., Muller H.W. The collagenous lesion scar—an obstacle for axonal 

regeneration in brain and spinal cord injury.Restorative Neurology & Neuroscience. 19(1– 

2):139–48, 2001. 87 Hermanns S., Reiprich P., Muller H.W. A reliable method to reduce collagen scar formation 

in the lesioned rat spinal cord.Journal of Neuroscience Methods. 110(1–2):141–6, 2001. 88Gilad G.M., Gilad V.H. Beta-aminopropionitrile treatment can accelerate recovery of mice 

after spinal cord injury.European Journal of Pharmacology. 430(1):69–72, 2001. 89Spilker M.H., Yannas I.V., Kostyk S.K., Norregaard T.V., Hsu H.P., Spector M. The effects 

of tubulation on healing and scar formation after transection of the adult rat spinal cord. Restorative Neurology & Neuroscience. 18(1):23–38, 2001. 90Pasterkamp R.J., Anderson P.N., Verhaagen J. Peripheral nerve injury fails to induce 

growth of lesioned ascending dorsal column axons into spinal cord scar tissue expressing the 

axon repellent Semaphorin3A.European Journal of Neuroscience. 13(3):457–71, 2001. 91 6. Edgerton V.R., Roy R.R., Hodgson J.A., Prober R.J., de Guzman C.P., de Leon R. Potential of adult mammalian lumbosacral spinal cord to execute and acquire improved locomotion 

in the absence of supraspinal input. J. Neurotrauma. 9 Suppl 1:S119–28, 1992. 92Fischer, F.R. and J.D. Peduzzi. Functional improvement in rats with chronic spinal cord injuries after exposure to an enriched environment. Soc. Neurosci. Abstr., 23:2188, 1997. 93 Neil Munro. SCIENCE: Petri-Dish Politics. National Journal, 04–19–2003. 

after SCI.81 IL–10 is neuroprotective after a spinal cord injury.82 Another study 

found that IL–10 and MPS reduce the amount of damaged tissue but do not change 

functional outcome.83

Inhibitors and Scar: For many years, Schwab and colleagues explored the potential of the IN–1 antibody to block myelin associated inhibitory molecule, Nogo, after 

SCI. IN–1 caused improvement in function if given shortly after injury.84 Other 

myelin-associated inhibitors such as MAG have been described. Blockers of Nogo 

and MAG appear to cause functional improvement.85 Many suggest that the scar 

inhibits 86 and have tried various inhibitors such as iron chelators.87 Betaaminopropionitrile treatment that inhibits the formation of glial scar accelerates recovery of mice after spinal cord injury.88 Other efforts involve implantation of a collagen tube to interfere with scar formation.89 The semaphorins may be important 

contributor to the inhibitory effects of the scar.90

Rehabilitation: There has been tremendous progress in the field of rehabilitation 

with use of weight-supported treadmills,91 functional electrical stimulation and biofeedback. In our own lab, we found a statistically significant improvement in rats 

with a moderate degree of spinal cord injury that are placed in an enriched environment compared to standard caging.92 An enriched environment consists of a social 

environment where there is free access to novel items that include exercise equipment. 

My primary reason for being here today is that I don’t want victims of injuries 

and diseases to again become victims. The best chance of cellular treatment for 

them is using their own stem cells. Victims of injuries and diseases are again being 

used to justify a treatment that is not in their best interest. Both the clinical trials 

and pre-clinical trials suggest that adult stem cells and/or using one’s own stem 

cells is a more effective treatment for diseases and injuries. The data just keep accumulating that this is the direction to go despite the fact that most of the research 

is being done using embryonic stem cells in experimental animals or human cell 

lines.93 The least funded area is still ‘bench to bedside’ research using one’s own 

stem cells or using adult stem cells. Despite the fact that there are much fewer experimental studies using adult stem cells, amazing progress has been made as evidenced by the clinical trials. The idea that we should look to cloning for a treatment 

for diseases or injuries is way in the future. Despite all the claims of its promise 

there has been only 1 or 2 experimental animal study to suggest that this is a promVerDate Nov 24 2008 06:41 May 20, 2013 Jkt 075679 PO 00000 Frm 00042 Fmt 6633 Sfmt 6621 S:\GPO\DOCS\80903.TXT JACKIE
39 

94 Rideout W.M. III, Hochedlinger K., Kyba M., Daley Q. and Jaenisch R. Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy Cell 109:17–27. 

ising direction.94 We have at least 200 experimental animal studies in the field of 

spinal cord injury alone that show that a particular cellular, growth factor, or other 

treatment causes a functional or anatomical improvement and only 1 or 2 in the 

field of cloning despite the fact that there is no ban on performing animal cloning. 

With only a limited amount of funding available, more focus is needed in directing 

research funds to areas that can help people in the next 5–10 years and not several 

lifetimes away. 

Senator BROWNBACK. Thank you, Dr. Peduzzi. 

We have a vote on. First, I want to announce that I’ll be joining 

other Members in a letter to promote and push for the funding for 

a national cord-blood bank system and the funding that you were 

talking about, Dr. Kurtzberg, that’s going to be needed to do this. 

I know Senator Hatch is going to be joining in this letter, and I 

think we’ll have several others. And we’ll also be helping with legislation on a national cord-blood banking program. I think this has 

extraordinary opportunities, and I really applaud your work and 

Dr. Rubinstein’s work that you’re doing in this field that really 

holds so much promise. It’s beautiful, beautiful work. And we’ll be 

pushing for that to see if we can’t get that mature on forward. 

This is very interesting to see and to hear, and exciting. I appreciate all of your passions and your help and your work that each 

of you are doing in this field. 

We’ve got a vote on that I’m going to move over for. And then 

what I think we’ll do is, we’ll bring the next panel up while I recess 

this for a period of time, and then bring that next panel up. 

But I hope, in the next year-and-a-half, we make as much 

progress as we made in the past year-and-a-half. I think you will 

see a fascinating array of people being treated and helped if we’re 

able to put in the resources here, if we’re able to really move forward in these fields of regenerative medicine. The adult work, the 

cord blood, has been beautiful in its successes and are really exciting to see these moving forward. 

We will be in recess for approximately 15 minutes. If I could 

have the next panel ready to go when I get back, and then we’ll 

move forward. 

Thank the panelists for being here today. 

We’re in recess for 15 minutes. 

[Recess.] 

Senator BROWNBACK. Call the hearing back to order. 

I want to apologize for making it over and back so fast, I didn’t 

have as much time to spend with those who wanted to visit with 

me. 

We’ve got an exciting next panel that I would like to call up. And 

the last panel was very informative, as well. These are patients, 

who have been working on and been involved in some really incredible things. Mr. Steven L. Barsh, from Pennsylvania; Mr. Keone 

Penn, from Snellville, Georgia; and Mr. Stephen R. Sprague, from 

Staten Island, New York, the people that will be testifying, and we 

look forward to hearing your comments and the testimony. 

I would say to each of you, we have your written testimony in 

the record, so you can summarize, if you’d like or you can go all 

go off this testimony, whichever you would like, or you can submit 

40 

your written testimony for the record and then say what you please 

here. And then I look forward to being able to question each of you 

for a little bit, if possible. 

I thank you all very much for coming here, appreciate your being 

willing to attend. And, Ms. Penn, I appreciate you being willing to 

come, accompanying your son, here today, as well. Mr. Barsh, delighted to have you. 

STATEMENT OF STEVEN L. BARSH, 

MERION STATION, PENNSYLVANIA 

Mr. BARSH. Thank you, Senator Brownback. And, by the way, do 

we have 5 minutes or 7 minutes for our testimony? 

Senator BROWNBACK. I’m going to run the clock at 7 minutes, 

just to give you some guidance. 

Mr. BARSH. No problem. 

Senator BROWNBACK. As you can see, it’s not a hard and fast 

rule, but it gives you a little bit of guidance. 

Mr. BARSH. It’s greatly appreciated. Unfortunately I’m not a patient; I’m a parent. Our son, Spencer, couldn’t be here today. He’s 

three and a half. It was too much for him to come down from Philadelphia, and he had some therapy this morning. So I’m just the 

parent of a patient. But good afternoon. 

Thank you for the opportunity to testify today on the very important topic of cord blood, and why a national cord-blood stem cell 

bank network should be provided for to save the lives of some of 

this great nation’s most severely ill children and adults. 

We first learned, a little over 2 years ago, that our one-year-old 

son, Spencer, had ALD, or adrenoleukodystrophy. In 50 percent of 

ALD children, more and more of their brains vanish due to this 

rare neurodegenerative disease, leading to loss of function and 

death by age ten. The remaining 50 percent have a severe-to-deadly form as adults. A parent’s worst nightmare, or, in this case, a 

day-mare, because you actually have to live through it. This is the 

disease behind the film, Lorenzo’s Oil, if you’re familiar with that 

film. As a matter of fact, Lorenzo’s father is in this room today, a 

very great man. 

Senator BROWNBACK. Would he care to stand so we could recognize him? 

Mr. BARSH. Oh, he’s just stepped out. Augusto Odone. I’m sorry. 

Senator BROWNBACK. Well, we’ll try to recognize him when he 

comes back. 

Mr. BARSH. I apologize. He is present today. A very great man. 

Spencer, our son, started to have repeated MRI brain studies. In 

February of last year, these MRI studies showed changes had started in his brain, indicating that the deadly brain deterioration had 

begun. 

Cord-blood and bone-marrow transplants are the only accepted 

therapies when this ALD brain deterioration begins and is caught 

in time, as Dr. Kurtzberg referenced. You need to catch these diseases in time. 

Via the National Marrow Donor Program, or the NMDP, we 

searched for a perfect six-out-of-six bone-marrow match, and 

couldn’t find one. And, as some of the doctors or researchers alluded to earlier, finding a good match is really important. OtherVerDate Nov 24 2008 06:41 May 20, 2013 Jkt 075679 PO 00000 Frm 00044 Fmt 6633 Sfmt 6601 S:\GPO\DOCS\80903.TXT JACKIE
41 

wise, particularly in bone marrow, it doesn’t work real well and it 

has a pretty poor outcome, to put it mildly. Plus, we were looking 

at nearly 6 months before we could even get Spencer to transplant, 

while his brain would continue to break down and deteriorate, because going the bone-marrow route takes a lot of time. 

See, even if you find someone on the National Marrow Donor 

Program donor list, it doesn’t mean you can get to them quickly. 

It’s a heartbreaking and gut-wrenching process of calling in potential donors that they identify through their network, having them 

screened, confirming that they’ll go through surgery to remove 

some of their bone marrow, et cetera. You lose precious time waiting. And in these neurodegenerative diseases, it’s a time issue. You 

really need to transplant very, very quickly. Worse yet, more than 

50 percent of people are turned away by the NMDP, told there’s 

no suitable donor for them. So about, you know, 50 to 60 of every 

100 people that knock on their door looking for a solution are told, 

‘‘Sorry, we can’t help you.’’ 

ALD, like many metabolic diseases, can move very quickly along 

its destructive path, and horrifying changes can often be seen daily 

in your child. This is particularly true for rare metabolic diseases 

discussed earlier, such as Hurlers, MLD, or metachromatic 

leukodystrophy, Tay-Sachs, and others—all diseases that can now 

be treated by a cord-blood transplant. 

In metabolic diseases, lessening the time to transplant equals 

less deficits and a better transplant outcome. As discussed, time is 

enemy number one. And, in cord blood, the unit has already been 

typed, checked, prepped, and is waiting in a freezer right now. 

There just needs to be more of it. 

Spencer’s pre-transplant work-up testing started just 4 weeks 

after we found a bad MRI of his brain, and only 5 days after my 

wife and I made the decision that he should be transplanted. There 

was no 6 months of waiting. We held on tightly to our two-and-ahalf-year-old son, Spencer, while he was in a pediatric isolation and 

intensive-care unit for nearly 40 days. There, he received his cordblood stem cell transplant, preceded by highly toxic medications, 

including massive, massive chemotherapy. He was lucky. He had 

what’s been considered and characterized an ‘‘easy course of transplant.’’ 

At the same time, we saw kids who didn’t make it, as the procedure proved too toxic. While core-blood stem cells work for most of 

their very, very fortunate recipients, more research needs to be 

done. More and higher-quality cord-blood units need to be available, not only for transplantation, but for research purposes. And 

stem cell research, in general, needs to be carefully and properly 

further explored to harness all of its life-saving potential. Those 

greater units and greater research, particularly in cord blood, 

would come about by passage of this bill. 

Spencer’s cord-blood transplant was just 14 months ago. But 

who’s counting? He’s doing extremely well. As a matter of fact, I’m 

happy to say he starts summer camp in 2 weeks. It’ll be his first 

time he ever goes to camp, school, nursery school, anything, in his 

entire life. And he’ll walk into that camp as a normal little boy. 

We see improvements and problem reversal on a weekly basis. At 

only 6 months post-transplant, physicians began to see improveVerDate Nov 24 2008 06:41 May 20, 2013 Jkt 075679 PO 00000 Frm 00045 Fmt 6633 Sfmt 6601 S:\GPO\DOCS\80903.TXT JACKIE
42 

ments in Spencer’s brain MRI, as well as his clinical presentation. 

It appears that Spencer is actually re-myelinating, meaning that 

the cord-blood stem cells are repairing his brain. The early progenitor stem cells from the cord blood are differentiating into other 

cell types. 

The MRI and clinical observations have been confirmed both at 

Duke and by a diverse team at Children’s Hospital of Philadelphia, 

or CHOP. I believe the non-technical word they have used is 

‘‘amazing,’’ going on to say, ‘‘We’ve never seen anything like this. 

We don’t usually see brain MRIs improve.’’ 

Cord blood works. With only one-tenth of the funding provided 

to the National Marrow Donor Program today, cord blood from a 

national cord-blood stem cell bank network is a solution for more 

than the 50 percent of people who the NMDP turns away. These 

treatment options must be available to the children and adults who 

have these devastating diseases, including malignant diseases, 

such as leukemias. 

In closing, it’s important to remember that you can get to transplant with cord blood extremely quickly, which is very, very critical 

with many diseases. The early progenitor stem cells in Spencer 

now appear to be differentiating into other cell types and are repairing problems in his brain. ‘‘Just amazing’’ is the term we hear 

time and again. 

At only one-tenth of the funding provided to the NMDP, a national cord-blood stem cell bank network can be provided so that 

this life-saving technology, that works today, can be available to everyone in need. 

We now have a normal and healthy 3-year-old son. His name is 

Spencer Barsh. And cord blood saved his life. 

Thank you for your time and thoughtful consideration on this 

matter. 

[The prepared statement of Mr. Barsh follows:] 

PREPARED STATEMENT OF STEVEN L. BARSH, MERION STATION, PENNSYLVANIA

Good afternoon. 

Thank you for the opportunity to testify today on the very important topic of cord 

blood and why a National Cord Blood Stem Cell Bank Network should be provided 

for to save the lives of some of this great nation’s most severely ill children and 

adults. 

We first learned a little over 2 years ago that our one year old son Spencer had 

ALD or Adrenoleukodystrophy. Fifty percent of ALD children have a deadly cerebral 

onset of this rare neurodegenerative disease leading to loss of function and death 

by age 10. The remaining 50 percent have a severe to deadly form as adults. A parent’s worst nightmare, this is the disease behind the film Lorenzo’s Oil. 

Spencer started to have repeated MRI brain studies and in February of last year, 

MRI studies showed changes had started in his brain indicating a deadly cerebral 

onset had begun. 

Cord blood and bone marrow transplants are the only ‘‘accepted’’ therapies when 

a cerebral onset of ALD has begun and is caught in time. 

Via the National Marrow Donor Program (NMDP) we had already been searching 

for a perfect 6/6 bone marrow match and couldn’t find one. Plus, we were looking 

at nearly 6 months before we could even get to transplant while Spencer would be 

deteriorating. 

Even if you find someone on the NMDP donor list, it doesn’t mean you can get 

to them quickly. It’s a heartbreaking and gut-wrenching process of calling in potential donors, having them screened, confirming they will go through surgery, etc. You 

lose precious time, waiting. Worse yet, more than 50 percent of people are turned 

away told there is no suitable donor for them. 

43 

ALD, like many metabolic diseases, can move very quickly along its destructive 

path and deficit changes can sometimes be seen daily. This is particularly true for 

rare metabolic diseases such as Hurler’s, MLD, Tay-Sachs, and others—all diseases 

that can now be treated by a cord blood transplant. 

In metabolic diseases, lessening the time to transplant equals less deficits and a 

better transplant outcome. Time is enemy #1. In cord blood, the unit has already 

been typed, checked, prepped, and is waiting in a freezer right now. 

Spencer’s pre-transplant work-up testing started just 4 weeks after his bad MRI 

(only 5 days after my wife and I made the decision that he should be transplanted). 

There was no 6 months of waiting. 

We held on tightly to our 21⁄2-year-old son Spencer while he was in a pediatric 

isolation and intensive care unit for nearly 40 days. There he received his cord blood 

stem cell transplant preceded by highly toxic medications including massive chemotherapy. He was lucky. He had what was considered an ‘‘easy course of transplant.’’ 

At the same time, we saw kids who didn’t make it as the procedure proved too 

toxic. While cord blood stem cells work for most of their very fortunate recipients, 

more research needs to be done. More and higher quality cord blood units need to 

be available not only for transplantation, but for research purposes; and stem cell 

research in general needs to be carefully and properly further explored to harness 

all of its life saving potential. 

His cord blood transplant was just 13 months ago, but who’s counting? 

He is doing extremely well. 

We see improvements and deficit reversal on a weekly basis. At only 6 months 

post transplant, physicians began to see improvements in Spencer’s MRIs as well as 

clinical presentation. 

It appears that Spencer is actually re-myelinating as the early progenitor stems 

cells from the cord blood are differentiating into other cells types in his brain. 

The MRI and clinical observations have been confirmed both at Duke and by a 

diverse team at the Children’s Hospital of Philadelphia (CHOP). I believe that the 

non-technical word they have used was ‘‘amazing’’ going on to say ‘‘They’ve never 

seen anything like this. We usually don’t see MRIs improve.’’ 

Cord blood works. 

With only 1⁄10 of the funding provided to the NMDP today, cord blood from a National Cord Blood Stem Cell Bank Network is a solution for the more than 50 percent of people who the NMDP turns away. 

These treatment options must be available to the children and adults who have 

these devastating diseases including malignant diseases. 

In closing: 

• It’s important to remember that you can get to transplant with cord blood extremely quickly which is very, very critical with many diseases. 

• The early progenitor stem cells in Spencer now appear to be differentiating into 

other cell types that are repairing problems in his brain. ‘‘Just amazing’’ is the 

term we hear time and again. 

• At only 1/10th of the funding provided to the NMDP, A National Cord Blood 

Stem Cell Bank Network can be provided for so that this life saving technology, 

that works today, can be available to everyone in need. 

We now have a normal 3 year old son. 

His name is Spencer Barsh. 

Cord blood, saved his life. 

Thank you for your time and thoughtful consideration. 

Senator BROWNBACK. Thank you for being here, Mr. Barsh. You 

know, when you talk about him going to summer camp, you amaze 

at the simple pleasures and what they truly mean. That’s a beautiful story. 

Mr. BARSH. We cherish every day. 

Senator BROWNBACK. Mr. Sprague, thank you very much for joining us here today, and I would turn to you next. 

44 

STATEMENT OF STEPHEN R. SPRAGUE, 

STATEN ISLAND, NEW YORK 

Mr. SPRAGUE. Thank you, Senator. 

I certainly am personally fortunate to have an opportunity to 

speak with you today; not in medical terms, but from a patient’s 

perspective. I know you can’t tell, but you’re looking at an aging 

baby-boomer. And I was already a medical veteran before I got my 

leukemia diagnosis. That was 7 years ago. I was 47 years old. I 

was a diabetic. I had survived a heart attack and bypass surgery, 

all in 1993. In spite of all that medical training, I was totally unprepared for a battle with cancer. 

This was in November 1995. In those days, chemotherapy only 

stalled the inevitable for long-term survival, and that was, of 

course, the traditional bone-marrow transplant. ‘‘The cure that can 

kill,’’ we like to call it. 

Although CML, which was my diagnosis, usually progresses 

slowly, in May 1997, only 18 months after my initial diagnosis, I 

found myself in blast crisis, the end-stage of the disease. 

Meanwhile, my oncologist began what would quickly become a 

very frustrating marrow-donor search. I soon discovered that less 

than a third of those seeking transplant have a matching sibling, 

the best and most obvious donor source. I was an only child. I 

needed to find an unrelated donor if a transplant were even to be 

an option for me. 

To make a very long story short, I was not one of the lucky ones 

to find a match in any of the marrow-donor registries. ‘‘Enjoy your 

remission for as long as you can. Get your affairs in order,’’ I remember them telling me, ‘‘while we keep looking and try to figure 

something else out.’’ 

This sad predicament is still all too familiar for many adult 

leukemians. Even now, far too many patients are unable to proceed 

to transplant due to the complexity, as you’ve heard already earlier—the complexity of antigen matching, as well as the problems 

inherent in tracking down, collecting the matching marrow from a 

hopefully still willing and still available marrow donor. 

Fortunately, as I was, unfortunately, beginning to lose my remission, my doctor was planning to begin one of the very first clinical 

trials for end-stage adult CML’ers using neonatal stem cells, those 

from cord blood. A perfect cord-blood match was found for me within days, from the New York Blood Center’s world-renowned Placental Blood Program, as it was known back at that time. And in 

life-or-death struggles like these, days do matter. 

Incredibly, some still anonymous New York City mother had decided to do what few mothers were doing back then, and that was 

to donate her newborn cord blood to a public cord-blood bank. It 

was that donation, from that newborn baby girl, that just happened 

to be my one and my only stem cell match. 

I entered the hospital October 30, 1997. Magic and miracles happened. And, by the grace of God, I was discharged 40 treacherous 

days later, but with a new, working immune system, no trace of 

leukemia. And no hair. 

[Laughter.] 

Mr. SPRAGUE. Here I am today, 5 years, 7 months, and 12 days 

later—and, believe me, I count every one of them—with a 100 perVerDate Nov 24 2008 06:41 May 20, 2013 Jkt 075679 PO 00000 Frm 00048 Fmt 6633 Sfmt 6601 S:\GPO\DOCS\80903.TXT JACKIE
45 

cent donor cells, all female chromosomes, just like my donor, completely cancer free. Still not much hair. 

[Laughter.] 

Mr. SPRAGUE. In my post-transplant years as a patient advocate, 

I’ve come to learn a lot of things—about myself, about life and 

death, about perspectives, about appreciations and priorities, but, 

most importantly, about hope. Part of that hope, for desperate patients seeking transplant, patients like I was, involves options. 

Heading down the transplant trail is a risky endeavor, even in the 

best of circumstances, but that critical first step can’t ever be taken 

without first finding the right stem cell match. Cord blood remains 

a largely untapped, non-controversial, readily available alternative 

source of non-embryonic stem cells. 

That’s the good news. That most of it continues to be trashed as 

medical waste instead of finding its way into a public cord-blood 

bank, that remains the problem. But it’s a solvable problem, as 

you’ve heard. 

Registering the good intentions of prospective volunteer marrow 

donors has been one solution to providing stem cells to patients in 

need. Collecting and preserving the actual cord blood, thanks to 

new parents who are willing, who are eager, to donate at the time 

of delivery, may be a better solution, or at least a viable option. 

As cord blood finds its way into the medical mainstream, it’s my 

personal hope, shared by my cancer companions—the lucky ones 

like me, as well as the less fortunate ones, who have died waiting 

while searching for their elusive marrow match—that an infrastructure to assist patients nationwide can be created, regulated, 

funded to take better advantage of this natural and precious gift 

of life. 

If more of those estimated 4 million new parents each year have 

a better opportunity to donate their newborn’s cord blood, an important new donor bank can be created quickly, conveniently, without pain and without controversy. And it certainly remains my 

privilege to serve as living proof of the promise of cord blood for 

the adult leukemia community. 

You know, we think of leukemia as a children’s disease, but 90 

percent of all leukemia cases are diagnosed in middle-aged adults, 

like me, like some of you. Regardless of age, cord blood is a proven 

alternative for saving lives, that needs your support to become 

more readily available. 

Again, I thank you for the privilege of telling my story and sharing my concerns. 

[The prepared statement of Mr. Sprague follows:] 

PREPARED STATEMENT OF STEPHEN R. SPRAGUE, CORD BLOOD CRUSADER, 

STATEN ISLAND, NEW YORK

Mr. Chairman and Members of the Subcommittee: 

My name is Stephen Sprague and I am personally fortunate to have the opportunity of speaking with you today. In a life before leukemia, I’ve appeared before 

lots of committees, but never about matters affecting life or death. Today, I’m here 

wearing a proud new hat . . . that of a long-term adult cord blood transplant survivor, and my remarks are much more critical . . . for those like me in the cancer 

community, and I hope, for you who have an opportunity to help us now . . . not 

with more research, but by supporting proven patient applications. 

46 

While you probably can’t tell, I’m an aging baby boomer and was already a medical veteran before I got my leukemia diagnosis 7 years ago at age 47. I’m a diabetic 

and had survived a heart attack and quadruple bypass surgery in 1993. In spite of 

that, I was totally unprepared for a battle with cancer. This was November 1995. 

In those days, and even today with new experimental wonder drugs for cancer, 

chemotherapy only stalled what was inevitable for long-term survival. . .the traditional bone marrow transplant. ‘‘The Cure That Can Kill’’ as some of us have 

learned to call it. Since CML is usually a slowly-progressing, manageable cancer, 

I continued to seek a decent quality-of-life while mentally preparing for transplant 

. . . the only option. For whatever reason, in May 1997, only 18 months after my 

initial diagnosis, I found myself in blast crisis, the end-stage of this disease. 

After a rigorous few months in the hospital, my oncologist, Dr. Andrew Pecora, 

got me into my first remission while we began what would quickly become a frustrating marrow donor search. I soon discovered that less than a third of those seeking transplant have a matching sibling, the best and most obvious donor source. 

Since I was an only child, I needed to find an unrelated matching donor if a transplant were to even be an option for me. To make a very long and complicated story 

short, I was not one of the lucky ones to find an acceptable match in any of the 

marrow donor registries. ‘‘Enjoy your remission for as long as you can and get your 

affairs in order’’ I was told, ‘‘while we keep looking and try to figure something else 

out.’’ 

This sad predicament is still an all-too-familiar one for many adult leukemians. 

Even now, far too many patients referred for a primary marrow donor search are 

unable to actually proceed to transplant due to the complexity of antigen matching, 

as well as the problems inherent in tracking down and eventually collecting the 

matching marrow from a hopefully still-willing and still-available donor. Fortunately for me, there soon came a series of events that, to this day, I find difficult 

to understand or describe. 

Just as I was beginning to lose my remission, my doctor, who directs Hackensack 

(NJ) University Medical Center’s prestigious Stem Cell Transplant Program, was 

planning to begin one of the very first clinical trials for end-stage adult CMLers 

using neonatal stem cells obtained from umbilical cord blood. And equally astonishing, a perfect cord blood match was found for me within days, from the New York 

Blood Center’s world-renowned Placental Blood Program, as it was known at the 

time. And in life-or-death struggles like these, days matter. Incredibly, some stillanonymous New York City mother had decided to do what few new mothers were 

doing back in those days . . . donating their newborn’s cord blood to a public cord 

blood bank. It was that donation from a newborn baby girl that happened to be my 

one and only match. 

I entered the hospital on October 30, 1997. Magic and miracles happened, including a pioneering treatment using cord blood. And by the grace of God, I was discharged 40 treacherous days later, December 8, 1997, with a new, working immune 

system and no trace of leukemia. And no hair. Fast-forward a bit and here I am 

today . . . 5 years, 7 months and 12 days later . . . with 100 percent donor cells, 

all-female chromosomes just like my donor, completely cancer-free and in relatively 

good health. And still not much hair. 

In my post-transplant activities as a patient advocate volunteer, I have come to 

learn a lot of things. . .about myself, about life and death, and about perspectives, 

appreciations and priorities. And most importantly, about hope. 

My point is simply this. Part of that hope for desperate patients seeking transplant . . . patients like I was . . . involves options. Heading down the transplant 

trail is a risky endeavor, even in the best of circumstances. But that critical first 

step can’t ever be taken without first finding the right stem cell match. 

As you will come to appreciate, umbilical cord blood remains a largely untapped, 

non-controversial and readily available alternative source of non-embryonic, neonatal stem cells. That’s the good news. That most of it continues to be trashed as 

medical waste instead of finding its way into a public cord blood bank remains the 

problem. A solvable problem. Registering the good intentions of prospective volunteer marrow donors has been one solution to providing stem cells to patients in 

need. Collecting and preserving the actual cord blood thanks to new parents willing 

and eager to donate at the time of delivery may be a better one. Or at least another 

viable option. 

As cord blood finds its way into the medical mainstream, it is my personal hope, 

shared by my cancer companions . . . the lucky ones as well as the less fortunate 

ones who have died searching for their elusive marrow match . . . that an infrastructure to assist patients nationwide can be created, regulated and funded to take 

better advantage of this natural and precious ‘‘gift of life.’’ If more of those estimated 4 million new parents each year have a better opportunity to donate their 

47 

newborn’s cord blood, an important new donor bank can be created quickly, conveniently, without pain, and without controversy. And it remains my privilege to serve 

as living proof of the promise of cord blood for the adult leukemia community. Although we think of it as a children’s disease, 90 percent of all leukemia cases are 

diagnosed in middle-aged adults. But regardless of age, cord blood is a proven alternative for saving lives that needs your support to become more readily available. 

Thank you for the opportunity to share my concerns with you and I would be 

happy to answer questions at the appropriate time. 

STEPHEN R. SPRAGUE, 

Cord Blood Crusader. 

Senator BROWNBACK. And thank you. What an encouraging 

story. 

Have you done any public-service announcements? Because 

you’ve got a natural gift here. 

[Laughter.] 

Mr. SPRAGUE. Oh, thank you, Senator. In a former life, life before 

leukemia, I appeared before lots of committees, but never on something about life or death. It was always about all the unimportant 

stuff. So I appreciate this opportunity. 

Senator BROWNBACK. We spend a lot of time on unimportant 

stuff. But we do spend some time on important things, as well. And 

you’re sitting next to quite a star. 

Mr. Penn, you’ve received quite notoriety, I know, already, you’re 

quite a remarkable young man. Will you tell us your story? 

STATEMENT OF KEONE PENN, SNELLVILLE, GEORGIA 

Mr. PENN. My name is Keone Penn. Two days ago, I turned 17. 

Five years ago, they said I wouldn’t live to be 17. 

I was born with sickle-cell anemia. My mother said I was a crying baby. She didn’t realize I was in pain. 

I had a stroke when I was 5 years old. The teacher called my 

mom from preschool and said that I had been acting funny all day. 

My mother knew the symptoms, because she had seen it with my 

grandparents. 

They had to do a blood exchange of my whole body. I had brain 

damage to the right side of my brain. I couldn’t walk or talk for 

a long time. I had to relearn everything. 

Things got worse after that. My life was full of pain crises, blood 

transfusions, and more times in the hospital than I can count. I 

was never able to have a normal life. I couldn’t play sports, like 

basketball or football. 

And I had a tube in my chest, and some kids bullied me and 

threatened to hit me in my chest, and I felt like an outsider, like 

I wasn’t a normal kid. And it was just hard. 

And I was suicidal then. Every day I’d go to school and people 

would pick on me. I couldn’t take it any more. One day, I came 

home from school with a sad look on my face. My sister got home 

after me, and my mom had went to work. I went in my room, sat 

on my bed, and cried. I had suicide on my mind. 

Then I thought about my family, how they would miss me. I 

thought about my mom, my sister, my aunt, and my cousin, how 

they would cry if I, you know, would die. I held my head up and 

dried my eyes. My mother always said we have to do what we have 

to do, and that you have to deal with the life you are given. 

48 

The year before I had the transplant, I was in the hospital 13 

times. I knew everybody in the hospital and had been in just about 

every room on the floor. 

Then my mom, one day when I was in the hospital, she came 

into the room, looking all depressed, because I had had a pain crisis. And she was really sad, and she just looked at me, and said, 

‘‘Keone, they want to try something. They want to do a cord-blood 

transplant. They said if you don’t do it in the next 5 years, you’re 

going to have another stroke that could be fatal. And this is experimental, and, you know, we have to work together on this.’’ And she 

said, ‘‘So what do you think? Do you want to do it?’’ And I was 

thinking I’d rather go out fighting than just wait and know you’re 

going to die, you know, because nobody wants to die. So I said yes, 

and we did the cord-blood transplant. 

My cord-blood transplant wasn’t easy, but I thank God I’m still 

here. I had a lot of problems, like graft versus host disease, which 

is a rejection of the new cells. 

I thought the coolest part about my transplant was that my 

blood type has changed from O to B. 

[Laughter.] 

Mr. PENN. I missed a lot of school, and I had to do a couple of 

years of home-schooling. But I still made all A’s and B’s. I made 

B’s this year. 

[Laughter.] 

Mr. PENN. Next year, I will graduate from high school. My family 

will be so proud to see me graduate, because they thought I 

wouldn’t live long enough to graduate. Before I had my transplant, 

they said I wouldn’t live another 5 years. 

My graduation will mark a big victory in my life. I want to become a chef. I plan to go to a good culinary arts school in Georgia. 

I cook for my family all the time. I think I’m pretty good at it. 

[Laughter.] 

Mr. PENN. My life, with sickle cell, was very rough. I have been 

through more things than most grownups can only imagine. But 

sickle cell is a part of my past. One year after my transplant, they 

pronounced me cured of sickle-cell anemia. Cord blood saved my 

life. Now I can look forward to a brighter future. 

Thank you. 

[The prepared statement of Mr. Penn follows:] 

PREPARED STATEMENT OF KEONE PENN, SNELLVILLE, GEORGIA

My name is Keone Penn. Two days ago, I turned 17 years old. Five years ago, 

they said I wouldn’t live to be 17. They said I’d be dead within 5 years. I was born 

with sickle cell anemia. Sickle cell is a very bad disease. I had a stroke when I was 

5 years old. Things got even worse after that. My life has been full of pain crises, 

blood transfusions every two weeks, and more times in the hospital than I can 

count. The year before I had my stem cell transplant, I was in the hospital 13 times. 

I never was able to have a normal life. My stem cell transplant was not easy, but 

I thank God that I’m still here. I will graduate from high school this year. I want 

to become a chef because I love to cook. I think I’m pretty good at it. Sickle cell 

is now a part of my past. One year after my transplant, I was pronounced cured. 

Stem cells saved my life. Thank you. 

Senator BROWNBACK. Thank you. 

Those are very impressive statements and very impressive comments. 

49 

Mr. Barsh and Mr. Sprague, I’m curious—and you may want to 

involve any of the researchers that can comment on this, as well. 

Senator BROWNBACK. You have commented that timing is critical 

determining the need for cord blood. Every minute, every day 

counts on this. 

Mr. Barsh, you were right on top of this at an early phase. How 

do we catch these earlier? What’s your advice on how we catch 

these to be able to intercept as fast as possible, number one? And 

I want to ask you, as well, is this the sort of thing if you catch it 

right at birth, you’re likelihood of success is far greater than if it 

drags on for a period of time? 

Mr. BARSH. Senator, they’re all excellent questions, and thank 

you for asking me, and I’ll just comment. 

One way that these types—or many, but not all—of the 

neurodegenerative diseases can be caught is by better prenatal 

testing—or testing, immediately after birth, like PKU testing, 

which is mandated today for every baby born. It’s done on a stateby-state basis, but not a Federal basis. In about a year, there’s 

going to be a test for adrenoleukodystrophy, so it could be screened 

and caught earlier. 

Ours was caught in a very unfortunate circumstance, where one 

of Spencer’s oldest cousins is in a persistent vegetative state from 

ALD today. There were three boys in our family that had it, because it’s X-linked and gets passed down. So Oliver was the martyr 

and won’t be able to recover, but he saved two other kids in the 

family. 

But better testing—— 

Senator BROWNBACK. I’m sorry—— 

Mr. BARSH. Yes? 

Senator BROWNBACK.—Mr. Barsh—— 

Mr. BARSH. Yes. 

Senator BROWNBACK.—let me back up on this a bit. What time 

was it caught in him? 

Mr. BARSH. He was about, I would say, seven or 8 years old, and 

he had been seeing physicians for about four or 5 years for some 

type of problem that had been misdiagnosed as everything—ADD, 

ADHD, Asperger’s Syndrome—which is very common with our type 

of disease. 

So I’d say I think the other thing that Congress could do would 

be to pass legislation, from a healthcare point of view—and I’ll just 

talk to one narrow area, which is children. Children that display 

some type of mental delay, or some type of symptom that wants to 

be diagnosed as ADD or ADHD—a very simple, painless MRI can 

be performed on their brains just to make sure it’s nothing else. 

In certain countries in Europe today—I believe, in France—it’s 

actually mandated. If a child has developmental delay, they do an 

MRI to check. That’s how you could catch a lot of these diseases, 

because they slip through. 

A typical pediatrician, our pediatrician, that has Spencer as a patient, that had ALD, she’ll never see another child in her career 

with the disease. Around one in 10–13,000 kids has ALD. And it’s 

so rare a single pediatrician would see it. 

So I think better education for physicians, and laws mandating 

that children that have some type of developmental delay be 

50 

screened. Again, screening right after birth for a number of these 

diseases—you know, West Virginia screens for two diseases. Pennsylvania screens for about 26. It differs state by state. 

Senator BROWNBACK. Can you screen before birth for ALD? 

Mr. BARSH. Yes, you can. You can screen at CVS testing. You can 

screen during amniocentesis. It’s not typically screened today, because, the genetic testing labs will tell you, ‘‘You can’t screen for 

everything. Otherwise, we’ll be screening for forever.’’ So they do 

it—if there’s a family history, they can absolutely screen for it 

today. 

Senator BROWNBACK. Are there treatments, even before birth? 

Are there in-utero treatments? 

Mr. BARSH. Not really. One of the things I believe some researchers are looking toward the future of doing in-utero cord-blood 

transplants, which, to me, is staggeringly interesting. But, yes, you 

could absolutely, if you knew. 

And that technology—it’s not there today, I believe. And I think 

Dr. Kurtzberg could address that specifically. But—— 

Senator BROWNBACK. Dr. Kurtzberg, would you mind sitting up 

here? I know this isn’t the way we normally proceed. And if any 

of the other researchers want to pitch in, but I really would like 

to get at this point, about at what age and stage can cord blood 

can be the most successful. 

Dr. KURTZBERG. Well, newborn screening could be available for 

most of these diseases. But it is not available on a routine basis 

or a mandatory basis. And even when parents request it, most of 

the time their pediatricians think it’s not indicated. But if it was 

part of the standard newborn screening panels, it would be wonderful. 

And what would be needed for that is, you know, an RFP to invite proposals to develop simple technology on dot-blot testing for 

newborn screening for these metabolic diseases. 

Senator BROWNBACK. Which do not exist today. 

Dr. KURTZBERG. Well, I mean, there are researchers working on 

the technology. It does exist, but it is not implemented in the 

United States, and it should be. Because all of these diseases would 

fare better if they were treated early in life. And regardless of what 

disease you’re treating, children do better with transplant earlier 

in life. We don’t have to use quite as much chemotherapy. They tolerate the procedure better. 

I don’t know if you remember, but our young Krabbe kids have 

100 percent survival because they’re healthier. And even though 

they have that bad disease, the rest of them can tolerate the therapy and the medicines easier. 

Senator BROWNBACK. What about in-utero diagnosis and treatment? 

Dr. KURTZBERG. Well, yes, there are—diagnosis is certainly possible. Parents can also be screened to see if they’re carriers so they 

know whether or not they would be possibly conceiving a child with 

the disease. There’s something called pre-implantation diagnosis, 

which allows selection of a healthy embryo. More commonly, people 

use CVS or amnio, as Steve mentioned, to make an in-utero diagnosis. 

51 

In-utero treatment is more complicated. There have been transplants tried in the second or third trimester. You obviously can’t 

give a fetus chemotherapy. And most of the time they’re either rejected because the fetus has enough of an immune system to not 

retain the cells; or there are too many cells, and the balances are 

off. 

What probably would work and has been demonstrated in animals is that if you did the transplant in the first trimester of pregnancy, which would require diagnosis by CVS, those cells would 

probably be tolerated by the fetus because it’s in a state called a 

pre-immune state. But no one knows that for sure, and a lot more 

research has to be done to prove that. But, theoretically, and in 

animals, that looks like the way to go. 

Senator BROWNBACK. We’re looking to set up a hearing on inutero treatments, because there’s a burgeoning field of treatments 

that—some spina bifida is being successfully treated in utero—that 

are really, really fantastic. 

Dr. KURTZBERG. Well, you would a 10- to 12-week fetus and inject cord-blood cells into the belly, or the forming abdomen, and 

those cells would induce tolerance so that, later, they could be 

boosted, after birth, without chemo. 

Senator BROWNBACK. Well, that’s interesting. 

Dr. KURTZBERG. But you have to know that the baby has the diagnosis, and that, again, has been done in animals, but not in people. 

Senator BROWNBACK. This procedure you’ve described has not 

been performed on people. 

Dr. KURTZBERG. No. 

Senator BROWNBACK. But it has been successful in an animal 

model. 

Dr. KURTZBERG. Correct. And there are people talking about implementing it in people. But it takes a lot of things to come together. I mean, you have to know there’s a risk, someone has to 

have a CBS, and then you have to be able to mobilize the donor 

in a week, which you could do with cord blood. 

Senator BROWNBACK. Mr. Sprague, in your treatment and the 

situation you’re in, what advice do you give to patient groups? You 

said you speak quite a bit. Is it early screening? Do we have to do 

more in the cord-blood field? Is it to look at the option of cord 

blood, which a lot of people don’t know about, instead of bone marrow? 

Mr. SPRAGUE. Early detection is kind of interesting for blood cancers. There are few symptoms. Usually the diagnosis is a total 

shock, because you don’t feel like you have cancer. You know you 

have a blood cancer, by a simple blood test. So one of the easiest 

things for everybody to do is just check your oil once in awhile. Get 

a blood test and make sure that everything is OK. Some of us do 

that religiously; some of us seldom do it. 

Once you’ve been diagnosed with a blood cancer, while chemotherapy will only keep the disease manageable—and, in some 

cases, for many, many years—it’s just known that the only cure— 

and leukemia is one of the few cancers that people can look you 

in the eye and tell you you’re cured—is a successful stem cell transplant. The problem, as I said earlier, is if you can’t find a stem cell 

52 

match, then you have no cure, and you sit home, and you wait to 

die. 

When you compare having to go through a marrow search with 

the ability to find a cord-blood match sitting on the shelf somewhere—already typed, already collected, already screened, already 

matched to your particular type—I mean, that’s going to save you 

months, sometimes more than months. And usually when patients 

decide to go to transplant, they’re in the serious stages of the disease. 

When you’re feeling pretty good and you’ve been early diagnosed 

with the leukemia, transplant is something you think is way down 

the line. So if you can improve the time to find a match by having 

an inventory of stored cord blood, as opposed to a bunch of people 

who have, out of the goodness of their heart, said, ‘‘I’ll be a donor 

if I match somebody and if you can find me when the time comes 

to get my marrow,’’ that’s going to save an awful lot of lives of 

blood cancer patients who are in distress to the point where if 

something doesn’t happen quick, then they’re going to die. 

Senator BROWNBACK. Mr. Penn, you’ve got quite a remarkable 

story that you’ve put forward in being cured of sickle cell anemia. 

What’s your advice to others that have suffered under the same 

disease that you’ve gone through? Is it to really seek to find cord 

blood that can match and that can do this and at earlier ages? 

Mr. PENN. Yes. Because, I mean, I can only imagine how hard 

it is on other people. And I’m just one kid with sickle cell. I mean, 

you could walk up to anybody today, and they could have sickle 

cell. They probably wouldn’t tell you, but—and there’s probably a 

lot of people in the world who have sickle cell and who are looking 

for a cure. And this could really help them. 

And if I could help them, I would like to. I mean, I’d do all I can 

to make sure nobody goes through what I went through. 

Senator BROWNBACK. How many years ago did you go through 

the procedure? 

Mr. PENN. Five years ago. 

Senator BROWNBACK. Five years ago. 

Mr. PENN. Yes, it’ll be 5 years on December 11. 

Senator BROWNBACK. And it was very difficult for you at that 

time, going through the chemotherapy and—— 

Mr. PENN. Yes. 

Senator BROWNBACK. Now, if this had been caught earlier and 

tried earlier, would that have been easier? 

Mr. PENN. Probably. Because your body’s more healthy when 

you’re a baby, so your body’s able to accept the chemotherapy when 

you have to do the chemo. And since my body had aged, my body 

really didn’t accept it that much. The cells either—since the cells 

had been in my body so long, they were fighting it off. That’s probably why I got graft versus host disease, too. 

Senator BROWNBACK. Dr. Kurtzberg, is this one that could have 

been—if you know and have a family history—diagnosed in utero, 

the procedure started that you had described? 

Dr. KURTZBERG. Certainly with the appropriate research on the 

procedure. But most states have screening programs for sickle cell 

in newborns, so it is pretty universally diagnosed at birth now. And 

medical therapy, like antibiotics and extra visits to the pediatrician 

53 

and education of parents about crises, et cetera, is started in the 

first year of life. If those babies were transplanted in the first year 

of life, one, they would tolerate it better, they would have a higher 

survival. They wouldn’t have damage to their tissues that sickle 

cell, itself, causes or the transfusions cause. So the whole process 

is easier. And, hearing Keone’s story, how he had to miss school 

and how, socially, he had issues because he was sick and he 

couldn’t attend school normally, are avoided when you transplant 

a newborn. Because by the time they recover, they’re two or one 

and a half, and they’re at a point where they really haven’t missed 

out on school or other social developmental things that older children need to have. 

Senator BROWNBACK. Is this being done regularly now in sickle 

cell diagnosis? Is the cord blood? 

Dr. KURTZBERG. The diagnosis is regular. Cord blood transplant 

is not regular. 

Senator BROWNBACK. Why not? 

Dr. KURTZBERG. Because, I think, the hematology community 

worries about the mortality risks. And there is a natural study of 

sickle cell disease, which is ongoing, which shows that not all patients will have a severe course. Some do and some don’t. And 

there have yet to be predictors identified that say which of the patients will be having strokes as children, et cetera. And so, because 

of that, there’s been a reluctance to recommend that all children 

with the disease are treated. 

And thalassemia, which is another hemoglobin problem where 

children don’t make red cells effectively at all and are dependent 

on transfusions from the age of about five or 6 months, there’s 

more acceptance to doing it in infancy because it’s known that that 

disease, because if iron buildup, will be fatal in usually the second 

or third decade of life. 

Senator BROWNBACK. Now, in Keone’s case, where at age five, 

had a stroke, he would be clearly be somebody that you would say 

we need to do the cord blood, with the knowledge that we have 

now. 

Dr. KURTZBERG. Right. Correct. And that is starting to happen. 

Yes. 

Senator BROWNBACK. Good. 

Dr. KURTZBERG. But, you know, just as a point, in some states, 

Medicaid won’t cover HLA typing for a sickle cell patient. That’s 

the tissue typing that you need to have to know: Do you have a 

donor in your family or do you need to look for an unrelated donor? 

So that’s not even a universal health care benefit, and it certainly 

should be. 

The other thing I wanted to say about genetic diseases is that 

parents are a huge resource, and they are huge advocates for their 

children. And as much as it’s important to educate pediatricians, 

of which I am one, I think that the parents can be empowered, in 

large part, to do a lot to get their children screened and to use tests 

that might be made available to them. And that parental education 

about some of these diseases would help make things happen. And 

with the Internet, there’s a huge tool now to bring about some programs that would be beneficial to all, and not that expensive to implement. 

54 

Senator BROWNBACK. Ms. Penn, do you have anything to tell us 

about your experience with this? 

Ms. PENN. Well, there’s quite a few things I could actually tell 

you. In Keone’s experience, his life has been pretty difficult with 

sickle cell. And, like he said earlier, if there’s a opportunity or a 

chance that another child doesn’t have to go through things that 

my child has been through, that’s a gift from God, and hopefully, 

this will bring about some change. 

Senator BROWNBACK. Yes. Hopefully, it will. 

Thank you very much. This has been a very encouraging group, 

all of you. You’ve been very thoughtful. 

I hope all of you do public service announcements, get the word 

out. I hope there’s lots of comments and quotes that are attributed 

to you, because I think this is the sort of thing we need to build 

a lot of knowledge and exposure to. This is a truly remarkable set 

of developments that—areas we hadn’t thought we had much 

hope—and a whole new alternative to be able to go with. 

I’m very heartened by this and by your comments. That’s another 

area for us to look at, is the Medicaid coverage on the sickle cell 

blood typing. 

Dr. KURTZBERG. HLA typing. Tissue typing or HLA typing. 

Senator BROWNBACK. OK. 

Well, thank you. God bless you all for coming forward. Thanks 

for being here. And hopefully we’ll make some good progress in this 

area. 

The hearing is adjourned. 

[Whereupon, at 4:33 p.m., the hearing was adjourned.] 

(55) 

A P P E N D I X 

TESTIMONY OF THE AMERICAN ACADEMY OF PHYSICIAN ASSISTANTS

On behalf of the more than 46,000 clinically practicing physician assistants in the 

United States, the American Academy of Physician Assistants is pleased to submit 

comments in response to the Subcommittee’s June 12 Hearing on Advances in Adult 

and Non-Embryonic Stem Cell Research. 

The Academy applauds the wonderful advances in adult and non-embryonic stem 

cell research that were highlighted in the Subcommittee’s hearing of June 12. The 

field of regenerative medicine does indeed offer great hope to individuals who are 

suffering from disease. However, to fully realize the enormous potential benefits in 

medical research and human healing, the AAPA believes that the use of human embryonic stem cell research, including the use of nuclear transplantation techniques 

(also known as non-reproductive, research or therapeutic cloning), must also be fully 

supported. The promises of human embryonic stem cell research are, through its 

eventual application in the hospital and office, to ease human suffering, save lives 

and harness fundamentally novel avenues for patient care. 

Physician Assistants (PAs) 

Physician assistants are legally regulated in all states to practice medicine as delegated by and with the supervision of a physician. Physicians may delegate to PAs 

those medical duties that are within the physician’s scope of practice and the PA’s 

training and experience, and are allowed by law. A physician assistant provides 

health care services that were traditionally only performed by a physician. Fortyseven states, the District of Columbia, and Guam authorize physicians to delegate 

prescriptive privileges to the PAs they supervise. An estimated 170 million patient 

visits were made to PAs and approximately 213 million medications were prescribed 

or recommended by PAs in 2001. 

PAs work in virtually every area of medicine and surgery and are covered providers of physician services through Medicare, Tri-Care, and most private insurance 

plans. Additionally, PAs are employed by the Federal Government to provide medical care, including the Department of Veterans Affairs, the Department of Defense, 

and the Public and Indian Health Services. 

American Academy of Physician Assistants (AAPA) 

The American Academy of Physician Assistants was founded in 1968 and is the 

only national organization representing physician assistants (PAs) in all medical 

specialties. The Academy educates the general public about the PA profession, 

assures competency of PAs through active involvement in the development of educational curricula and accreditation of PA programs, provides continuing education, 

and conducts PA-related research. The mission of the Academy is to promote quality, cost-effective health care, and the professional and personal growth of physician 

assistants. 

AAPA Policy on Stem Cell Research 

The AAPA’s policy on stem cell research is based on the desire to promote the 

intense, vigorous, and responsible scientific research that will be necessary to realize the potential medical benefits of using stem cells to treat disease and repair tissue damaged by disease or trauma. The research holds tremendous promise for the 

development of new treatments for a wide range of serious illness and injury, such 

as Parkinson’s disease, Alzheimer’s disease, cancer, diabetes, heart disease, arthritis, neurodegenerative and immunodeficiency diseases, and spinal cord injury. 

The AAPA policy on stem cell research was adopted by the Academy’s House of 

Delegates in 2002 and 2003. Four principles are core to the Academy’s collective policy— 

• Federal funding must be used to support embryonic stem cell research. 

56 

• Productive research requires a larger source of stem cell lines than those in existence on August 9, 2001, necessitating the isolation of new embryonic cell 

lines. 

• The cloning of human beings for the purpose of reproduction must be prohibited. 

• The use of nuclear transplantation techniques should be promoted as a desirable means to create embryonic stem cells for research purposes. 

The AAPA believes the Federal government is the single, best source for the large 

and sustained financial investment needed to move the research forward. The Federal government must play an important role in providing public review, approval, 

and monitoring of the research, as well as insuring the scientific and ethical appropriateness of the research. 

Concerns regarding the age, quality, ownership, and racial and ethnic variability 

of the cell lines available on or before August 9, 2001 led the AAPA to support the 

isolation of new embryonic cell lines. Questions about whether appropriate informed 

consent from the donors of embryos that had been used to develop the earlier cell 

lines further substantiated the need to support the isolation of new embryonic cell 

lines. 

In developing its support for embryonic stem cell research, the Academy addressed difficult ethical considerations, which led to policy being adopted to safeguard the use of donated embryos, including the appropriate use of excess, abandoned, or non-transferable frozen embryos currently stored at in vitro fertilization 

clinics. 

In 2003, the AAPA affirmed and strengthened its opposition to the inappropriate 

use of human embryos by adopting policy to support a legally enforceable ban on 

the cloning of human beings for the purpose of reproduction. 

The creation of stem cells by nuclear transplantation is supported as an ethically 

responsible means of isolating new embryonic stem cell lines, because the procedure 

does not involve implantation of a blastocyst in a uterus, nor is it intended to lead 

to the birth of a cloned human being. The stem cells that are produced are 

unspecialized cells that can renew themselves indefinitely and, under the right conditions, develop into more mature cells with specialized functions. Furthermore, the 

cells are created with the express permission of the donor and the express understanding that the tissue will be used for stem cell derivation only, not for implantation and reproduction. 

The AAPA believes that stem cell research and nuclear transplantation hold tremendous potential to ease human suffering through advanced therapies. The Academy applauds the Subcommittee’s use of the June 12 hearing to showcase the remarkable advances in medicine that have been made in the fields of adult and nonembryonic stem cell research. However, the Academy also urges the Subcommittee 

to consider the appropriate and responsible use of embryonic stem cell research. No 

other current avenue of medical research holds the promise of human embryonic 

stem cells. 

Thank you for the opportunity to submit the comments of the American Academy 

of Physician Assistants to the Hearing Record. 

Æ