CiRA Foundation Activity Report

2 0 2 3. 127vol.

Message
The CiRA Foundation is now in its fourth year.
Through our main project, the iPS Cell Stock Project, we have
distributed iPS cells to more than 70 research institutes andcompanies, and more than 10 of these projects have used ouriPS cells in clinical trials, with some having conﬁrmed alreadythe safety and eﬃcacy of the treatment.
Since September 2023, the CiRA Foundation has been
participating as a subcontractor for a new program related toregenerative medicine operated by the Center for iPS Cell
Research and Application, Kyoto University. This program will
receive government support for ﬁve years.
Also in 2023, in addition to our usual donations, the campaign,"Deliver iPS Cells to Everyone", received generous support forour work. I sincerely thank all of our donors.
In order to meet your expectations, the entire staﬀ willcontinue our eﬀorts toward the practical use of iPS cells.

Shinya Yamanaka
President

Crowdfunding report on the "Deliver iPS Cells to Everyone" campaign.
From September 6, 2023, to November 20, 2023, the CiRA Foundation held the "Deliver iPS Cells toEveryone" campaign to recruit 1,000 monthly donors in Japan. Ultimately, we received support from2,748 donors, plus 115 donors who increased their monthly donations.
During this period, we also held online events to inform everyone about our activities: the threelectures in total provided basic knowledge on iPS cells, research ethics, and quality control methods
for iPS cells.
In addition, we received many messages of hope for theclinical application of iPS cell technology, such as"I hope for the development of research" and "I want tosupport a future in which many incurable diseases will
be cured".
We would like to express our sincere gratitude for yourstrong support. With our supportersʼ thoughts andexpectations in mind, we will continue our eﬀorts to"deliver iPS cells to everyone". (Philanthropy Oﬃce)

01

Thank you so muchfor your support

What is the HLA genome-edited iPS cell stock?

The CiRA Foundation began providing clinical grade cells - "HLA genome-edited iPS cell stock"in June 2023. This stock has a lower risk of an immune reaction when used in a cell therapy.
Below is some information about their special properties.

Pre-manufactured and stockpiled iPS cell stock
The "HLA-homozygous iPS cell stock" provided by the CiRA Foundation was created withthe cooperation of the Japanese Red Cross Society, the Japan Marrow Donor Program, andthe Cord Blood Bank, with the help of blood donors who are homozygous at three HLA loci(an immune type of combination that is less likely to cause immune reactions.)
When used in regenerative medicine, iPS cells are diﬀerentiated before transplanted intopatients. However, it takes nearly a year and costs tens of millions of yen to produce one
iPS cell stock. Shortening that time and cost is why multiple iPS cell stocks have been prepared by the CiRA Foundation.

More patients eligible for treatment
At the CiRA Foundation, we envision afuture in which iPS cell stocks are used as
raw material for cell therapies, not only forpatients in Japan but throughout the world.
To match the immune types of morepatients, we have turned our attention togenome editing technology, which wasawarded the Nobel Prize in Chemistry in2020. Genome editing technology uses anenzyme that acts as molecular scissors tocut DNA and rewrite genetic information. Itis a popular technique in many laboratories
around the world and is used not only in
medical research but also in many otherﬁelds, including agriculture and ﬁsheries.

HLA homozygous donor

HLA (human leukocyteantigen) type↓
iPS cell manufacturing↓

Genome editing

Enzyme↓Using this technology, we generated the"HLA genome-edited iPS cell stock" from
HLA homozygous iPS cell stocks.

Cells for transplantation

Although this HLA genome-edited iPS cellstock has great potential, it has not yet
been used in any clinical trial. We are planning to conduct more research on the safety
and eﬃcacy of these cells through joint
research with universities and companies towhich we provide iPS cells.
We will continue our research and development to provide better iPS cells by integrating new technologies.

02A

B

C

D

E

F

G

Even if the HLA type is not the same as that of the donor,
as in the case of patients C, E, and G, the risk of an immune
reaction will be smaller if using genome editing technology.

Working at the CiRA Foundation

Teamwork across departments!

Secretariat of the iPS Cell Stock Review Committee
０What exactly do you do before distributing iPS cells?

There are many things to do and many people involved in the iPS cellstock distribution process, such as checking details of the organizationthat wishes to obtain iPS cell stock and contracting with partnering
institutions. We interviewed the staﬀ in charge of the work.

Q
1

iPS cell stock is manufactured and stockpiledby the CiRA Foundation. Why does it take several
months from request to distribution?

We are committed to expeditious procedures topromote research. On the other hand, the iPS cellstock is made from the blood of healthy donors andcontains a lot of personal genetic information about
the donors, so it must be handled with care.

Q Are there any precautions that should be taken when
4 sending cells to research institutions or companies?
The provided iPS cell stock will be transplanted into
patients after cell diﬀerentiation. The iPS cell stock
must be stored with a certain level of quality inanticipation of the eventual administration of thecells to humans in clinical trials.

We take the utmost measures to ensure that theprivacy of donors is not compromised after thedistributed iPS cell stock leaves the CiRA Foundation.

Q2

How exactly do you protect privacy?

During the period between the production of the iPS
cells and their distribution, the cells are stored inliquid nitrogen tanks at temperatures between -150
and -190 oC to preserve the quality. Otherwise, theycannot be used for the transplantation or research.
This temperature must be maintained during thetransport from departure to arrival, too.

The ﬁrst distribution of an iPS cell stock was made in
the summer of 2015, before the CiRA Foundation wasestablished. At that time, the basic policy and review
criteria for the distribution were established, and an
iPS Cell Stock Review Committee was set up.
The committee checks the following and otherpoints of the institutions requesting the cells. 1) Are
they likely to contribute to the development ofregenerative medicine for the beneﬁt of patientssuﬀering from illness or injury? 2) Are they conducting research and development that has the potential
to lead to new therapies? 3) Can the cells be usedappropriately by them? Only if satisfying these andother questions do we provide the iPS cell stock.

Q
3

For the shipment of cells, we coordinate the shipping
schedule, arrange the containers, and make arrangements with the carrier.
In addition, when exporting cells or providing technology overseas, we carry out security trade control
procedures within the CiRA Foundation in accordance with the relevant laws and regulations.

Q
5

What is the role of the secretariat of
the iPS Cell Stock Review Committee?

Please tell us about the challenges andrewards of your daily work.

Even after working hard and meticulously preparing
the cell shipments, unexpected events occur.
In the past, there was a case in which the iPS cells
were not delivered properly due to a problem withthe local customs. It was very frustrating that iPS cells
produced from donor blood could not be delivered.

The secretariat conﬁrms information on institutions
that wish to obtain the iPS cell stock and coordinates
between the iPS Cell Stock Review Committee, which
decides whether or not to provide the cells, and theinstitutions that wish to obtain the iPS cell stock,
including arrangements for the cell transportation.

Based on this experience, even after the cells leave
Japan and are entrusted to a carrier, we, the secretariat, check the status of the cells until they actually
arrive at the recipient institution. We do not rest until
we receive word from the recipient institution thatthe cells have arrived safely and are being cultured
without problems.

In order to ensure that the process goes smoothly
and trouble-free, a contract is concluded in advancewith the organization to which the cells will beprovided. This process involves building a relationship of trust between the organizations and involves
thorough discussions and document exchange toreach a mutual agreement. It is not unusual for theprocess to take several months or more.

When we receive a report of the safe arrival andprogressing research, we are happy to know that ouractivities made an impact.
03

NewsJune 2023

CiRA Foundation booth at ISSCR

T h e In ter n at io nal So c ie t y f o r St e m Ce ll Re s e arc h( ISSCR ) , th e large s t annu al gat he rin g of s t e mcell r esear c he rs in t he w o rld, w as he ld
J un e 14-17 in B o s t o n, U SA.
We exhibited a booth to inform about ouractivities, and our researchers presented
their research results.

October 2023

Canon EXPO 2023

An exhibition introducing new products and future technologies of the CanonG r o u p w a s h e l d i n Yo k o h a m a f r o m O c t o b e r 1 8 t o 2 0 . A m o d e l o f t h e i r a u t o m a t e dautologous iPS cell production system, which is being developed in collaboration
with the CiRA Foundation, was displayed.
Our staﬀ members attended the exhibition and discussed future developments.
It was a valuable opportunity for the CiRA Foundation, as many people deepened
their understanding about us through the exhibition.

December 2023

Regenerative Medicine Open Innovation Seminar 2023

W e h e l d a s e m i n a r i n a s s o c i a t i o n w i t h t h e K a n s a i B u r e a u o f E c o n o m y, C i t y o f K y o t o ,Tr a d e a n d I n d u s t r y ( K a n s a i R e g e n e r a t i v e M e d i c i n e I n d u s t r i a l C o n s o r t i u m : K R I C ) ,A d v a n c e d S c i e n c e , Te c h n o l o g y & M a n a g e m e n t R e s e a r c h I n s t i t u t e o f K y o t o ( A S T E M ) ,a n d t h e K y o t o M u n i c i p a l I n s t i t u t e o f I n d u s t r i a l Te c h n o l o g y a n d C u l t u r e .
The seminar targeted companies interested in joint
research with us. Approximately 50 people attended.

CiRA Foundation Activity Report
Published on December 12, 2023

vol.7

CiRA Foundation
53 Shogoin kawahara-cho,

Sakyo-ku, Kyoto 606-8397, Japan.

https://www.cira-foundation.or.jp