CiRA Foundation

CiRA Foundation
Activity Report

July, 2022

Message

Cooperating with various organizations
for the practical application of iPS cells
On April 1, 2020, we began the CiRA Foundation andare now into our third year. Over this time there has
been a consistent increase in research institutions andcompanies using iPS cells manufactured by the CiRA
Foundation. They also use our outsourced services forquality evaluation. And this year we made the ﬁrst
shipment of our iPS cell stock to an overseas university.

In Japan, clinical research using iPS cells continues toTo realize the practical application of regenerative
medicine using iPS cells, universities need to cooperatewith industry. It is also vital for more companies toco ntr ib u te to th e res earch an d d eve l o p m ent ofregenerative medicine. To encourage more companies
to join this eﬀort, the CiRA Foundation has launched
the “P.S. i LOVE YOU” PROJECT with 19 participatingcompanies and is actively communicating about its
work.

supporting research and development as much as possible

progress. Notably, regarding clinical research results fortransplantation medicine, the research group led by ProfessorKohji Nishida at the Graduate School of Medicine, Osaka

University has reported that the transplantation of iPS-cellderived corneal epithelium works well for visual recovery.

However, the speed of iPS cell research diﬀers for each disease
and each disorder. T he CiR A Foundation is devote d totoward the practical application of iPS cell-based medicine.

T h e re s earch an d d eve l o p m e nt o f re g e n e r ati ve
medicine using new iPS cell-based medical
technologies are very costly both in terms of money
and time. For most companies, entering this ﬁeld
entails a signiﬁcant risk. To lower the entry barriers forcompanies, the CiRA Foundation provides iPS cells andrelevant technologies at aﬀordable prices. On behalf ofall of us at the CiRA Foundation, I want to thank ourd o n o r s a n d t h e m a ny p e o p l e w h o s u p p o r t o u ractivities.

Shinya YAMANAKA

Representative Director
CiRA Foundation

Activity Report 1

Realizing the development of iPS cell-based therapies
for cerebral infarction
The CiRA Foundation is participating in a joint research project that is developing therapies for cerebral infarction.
This project is in partnership with the research group led by Professor Jun Takahashi. This April, Professor Takahashi
became Director of the Center for iPS Cell Research and Application (CiRA), Kyoto University.

T h e Ta k a h a s h i l a b o r a t o r y i s r e s e a r c h i n g
intractable neurological diseases using iPS cells.
In 2018, they began a physician-initiated trial for
Parkinsonʼ s disease with physicians at Kyoto
University Hospital. Seven patients have received
the cell transplantation as scheduled, and theirhealth conditions are under observation.
We manufactured the dopaminergic progenitors
used in this trial at our cell preparation facility(Facility for iPS Cell Therapy, or FiT).
Following this work, Professor Takahashi and his
team are using iPS cells to developtransplantation therapies for cerebral infarction.
We are responsible for manufacturing the cells
derived from the iPS cells for the transplantation,
the quality evaluation of the cells, the oﬀering
a n d m a na g e m e nt o f c l ea n ce ll p r o du c t i o nfacilities, and the consultation for the clinicalapplication, among other aspects associated withthe project.
To realize cell transplantation to patients, themanufacturing of cells is a critical ﬁrst step.
We manufacture cells at FiT, which oﬀers a clean
environment that fulﬁls conditions above thosefound in experimental laboratories. Materials andmachines commonly used in experimentlaboratories are rarely applicable for themanufacturing of cells to be used intransplantation therapies.
Compared with iPS cells for research use, themanufac turing of iPS cells for clinical use ischallenging. We have accumulated expertise andequipment for this purpose. We are committed toworking with the Takahashi laboratory and others
like it to provide iPS cell technologies to patientsin need as quickly as possible.

Jun TAKAHASHI

Director and Professor,Center for iPS Cell Research andApplication (CiRA), Kyoto University(Director, CiRA Foundation)
We have manufactured cells for a clinical trial with the CiRA
Foundation. We have great conﬁdence in the CiRA Foundationand are happy to work with them again and again. Its
contributions have been critical for us overcoming the manychallenges of developing new therapies. The technology andexpertise we obtained by working with the CiRA Foundation on
the cell production for our Parkinsonʼ s disease clinical trial are agreat asset to us. For cerebral infarction, the types of cells andclinical conditions diﬀer. We will therefore face new challenges,
but I am certain we can overcome them by working together.

Daisuke DOI

Junior Associate Professor,
Center for iPS Cell Research andApplication (CiRA), Kyoto University

We develop e d new cell - b ase d prep arations for celltransplantation therapies for Parkinsonʼ s disease and now for
cerebrovascular disorders such as cerebral infarction (or stroke).
Our experience with Parkinsonʼ s disease has been a great
advantage for our work on cerebral infarction, but there are also
m a ny d i ﬀ e r e n t c h a l l e n g e s . Co o p e r a t i n g w i t h t h e C i R A
Foundation gives us conﬁdence that we will develop new
therapies for patients in need.

Tomoko ICHISAKAManager,
Manufacturing Control Unit, Manufacturing Section
CiRA Foundation
In general, for any clinical trial, many people are involved in theprojec t, including hospital staﬀ and the patient. All thesestakeholders must work together. The Manufacturing Section is
crucial for devising the best strategy for the cell production. We
are motivated by hearing of successful cell transplantations andimproved patient health.

Activities

Activities of the CiRA Foundation
Clinical Applications
September 2021

Transplantation of natural killer cells
for ovarian cancer treatment

Natural killer cells produced from our iPS cellstock were administered to patients suﬀeringfrom ovarian clear cell adenocarcinoma as
par t of the clinical trial conduc ted by theresearch group led by Professor Shin Kaneko
at the Center for iPS Cell Research andA p p l i c at i o n (C i R A), Ky o to Un i ve r s i t y, i ncollaboration with the National Cancer Center
Hospital East.

December 2021

Transplantation of neural precursor cells
for spinal cord injury
Neural precursor cells produced from our iPS
cell stock have been administered to patientssuﬀering from spinal cord injury as part of theclinical research conducted at Keio University
Hospital. In March 2022, the safety of the cells
was conﬁrmed.

April 2022

Transplantation of
corneal epithelial cell sheetsfor visual recovery

Corneal epithelial cell sheets produced from
our iPS cell stock were transplanted topatients suﬀering from exhausted corneal
epithelial stem cells, a condition that leads topoor vision. Osaka University reported thatthe visual acuity of three patients improved
signiﬁcantly in one year. (A fourth patient had
develop e d cat arac t s, mak ing evaluation
d i ﬃ c u l t .) F o r o n e p a t i e n t , v i s u a l a c u i t y
improved from 0.15 to 0.7.

April 2022

Transplantation of iPS cell-derived
platelets for thrombocytopenia

The Megakaryon Corporation has
manufac tured platelets from our iPS cellstock. These platelets were transplanted into
patients with thrombocytopenia. Evaluationof the eﬃcacy and safet y is ongoing.
Megakar yon is now in discussion with theproper authorities to license the cells as acommercial product.

July 2021

Introducing the CiRA Foundation online
The Center for iPS Cell Research and Application (CiRA),
Kyoto Un i ve r s i t y, f r o m w h i c h t h e C i R A Fo u n d at i o nspawned, regularly holds tours of its facilities. A recent
online tour included our Facility for iPS Cell Therapy (FiT).
※P l e a s e u s e t h e Q R c o d e t o s e e t h e v i d e o .
※Language : Japanese only

Basic agreement with VCCT, Inc.

October 2021

Joint research agreement with
CellFiber, Co., Ltd.

November 2021

We signed a basic agreement with VCCT, Inc., for thedevelopment of medical therapies for retinal diseases.
The agreement includes research information sharing andthe provision of material in order to advance the my iPS
Project.

To accelerate our adoption of automated cell culture
systems for cell banking, we are using the companyʼ sunique technology called CellFiber, which enables themass cultivation of cells at less cost. As of June 2022, partof the veriﬁcation process was completed.

Regenerative Medicine Open Innovation Seminar December 2021

We held a seminar in association with the Kansai Bureauof Economy, Trade and Industry (METI) , Kyoto City and theAdvanced Science, Technology & Management ResearchInstitute (ASTEM). The seminar targeted companies
interested in joint research with us. More than 70 people
attended.

Joint research agreement with National Yang Ming Chiao Tung
University (Taiwan)
We signed a joint research agreementwith the university to develop newtechnology for iPS cell production
using the expertise and technologyof the two institutions. The agreement
includes sending one of our staﬀ to theuniversity for a speciﬁed period.

January 2022

First shipment of our iPS cell stock
for clinical use to an overseas partner

March 2022

Yuko KITANO wins the Hanamizuki Prizefor her work on the my iPS Project

April 2022

We provided our iPS cell stock for clinical use to iPS Bio,Inc., a start-up stem cell company in Korea. This was theﬁrst shipment of our iPS cell stock for clinical use to an
overseas company. We aim to send our cells to morecompanies around the world.

This prize is awarded annually to recognize theexceptional work of one of our staﬀ. This year, Yuko
Kitano won the Hanamizuki Prize for her work to expand
iPS cells and diﬀerentiate them to myocardial lineages inﬂoating culture.

A day in the life of members of the CiRA Foundation

The Quality Test Team ofthe Quality Section

The Quality Section evaluates and assures the qualityof iPS cells manufactured by the CiRA Foundation andthe quality of cells for transplantation produced using
iPS cells.
They evaluate various items regarding cells, including
the genomics, characteristics, and contamination(s terilit y). We also conﬁrm the condition of thereagents and the materials used for iPS cell
production.
In this article, we describe the daily work of threemembers from the Quality Test Team. Their work iscritical, as they check on bacterial infection in the cells
or in the production area (the number of bacteria
must be controlled within deﬁned limits).
iPS ce lls an d oth e r ce lls p ro du ce d by t h e CiR A
Foundation are all living cells. Therefore, we cannot
apply sterilization treatments or processes typicallyused for drugs and medicines, which makes bacteria a
critical issue. It is very important to prevent bacteria
contamination at all stages of the cell production andall the way to the shipment of the cell product. For
every process, such as replacement of the iPS cell
culture solution and transfer of iPS cells from one
culture dish to another culture dish, we extract part ofthe culture solution and test it for bac teria
contamination.

FiT (Facility for iPS Cell Therapy)
Production of iPS cells andother cells for clinical use

In the cell production area, a permissible number ofbac teria per speciﬁed area is deﬁned for eachprocess. Appropriate control is necessary to prevent
bacterial contamination. To conﬁrm the number ofbacteria, we collect bacteria ﬂoating in the air oradhering to surfaces, like desks and machines. We
cultivate them for several days and then check their
number and type. Based on criteria, we can thenconclude if bacteria in the cell production area havebeen controlled appropriately. While many of ourcolleagues focus on iPS cells, our attention is on
microorganisms.
Most types of cells for transplantation are unusable
once they are frozen. Therefore, the cells must be
delivered shortly af ter their production, whichmeans we have to test them by using special
method late into the night and ﬁnish our reportsby the next morning. Although the work can feel
tedious at times and is sometimes diﬃcult, it isessential for us to assure the quality of the cells wedeliver. The work also gives us great satisfaction,
because these cells are being used in clinical testing
and clinical trials. We are all committed to assuring
the quality of the cells.
Saki TOMITA

Kyoka HIGUCHIThe appearanceof bacteria!

Quality Section (Evaluate and assess
the quality of the manufactured cells)
Quality Assurance Unit
GenomeAnalysis
Team

Quality Control Unit

Quality Test Team Quality ControlManagementTeamOur Team!

CiRA Foundation
Activity Report vol.4
Published on July 28, 2022

Mie YAMAMOTOCiRA Foundation

53 Shogoin kawahara-cho,
Sakyo-ku, Kyoto 606-8397, Japan.

www.cira-foundation.or.jp