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Recent Progress in iPS Cell
Research and Application
Shinya Yamanaka, M.D., Ph.D.Center for iPS Cell Research and Application (CiRA), Kyoto University, Japan
Takeda - CiRA Joint Program, Shonan, Japan
Gladstone Institutes, San Francisco, USA
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1989
¥55,000/Tab
($500/Tab)
By PhD Dre at en.wikipedia, CC BY-SA 3.0,
https://commons.wikimedia.org/w/index.php?curid=3247145
Science Overcoming Diseases
25 yrs.
2014
Photo courtesy of Gilead Sciences K.K.
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iPS CellSkin cells
(induced Pluripotent Stem cell)
Human
2007
Mouse
2006
The Discovery of iPS Cells
Oct3/4 Sox2 Klf4 c-Myc
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The Features of iPS Cells
Proliferate infinitely
Differentiate into many types of cells
(Pluripotency)
Blood cells
Pancreatic cells
Neurons
Heart muscle cells
Muscle cells
Cartilage cells
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iPS Cells
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Heart Muscle Cells
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The Applications of iPS Cells
Neurons
Skin cells
Blood cells
Regenerative
Medicine
Drug
Development
iPS cells
Muscle cellsHeart
Muscle cells
Cartilage
cells
Reprogramming
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Retinal Cells
World’s first Transplant in Human (2014)
Age-related Macular Degeneration
Dr. Masayo Takahashi
(RIKEN, CDB)(Photo by RIKEN)
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iPS cells
Qualitycheck
Differentiatedcells
Qualitycheck
Sample
collection
Autologous iPS Cells
Autograft: Too expensive and time-consuming
iPS Cell Stock for Regenerative Medicine
Transplantation
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HLA homozygous donor
HLA Homozygous “Super” Donors
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Okita et al., Nature Methods, 2011
90%
80%
0%
50%
100%
Pro
po
rtio
n o
f m
atc
he
d p
op
ula
tio
n
No. of unique HLA-homozygous donors
0 50 100 150 200 250
One donor covers ~17%
of all the Japanese population!
How Many HLA Homo Donors Are Required?
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200
100
03.7 x 104
6.4 x 104
1.6 x 105
140th
75th
50th
0 5 10 15 20
Screening numbers (x 104)
No
. of H
LA h
om
o d
on
ors
Data provided by Dr. Hiroo Saji
How Many Screenings Are Required?
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Distribution started from
2015
Clinical-grade iPS
CellsQuality
Check
Cell Processing Facility (CiRA, FiT)
Stock
Japanese Red
Cross Society
Platelet /
Bone Marrow
Donors
Cord Blood Banks
Informed Consent &
Blood Sampling
“HLA HomozygousDonors”
iPS Cell Stock for Regenerative Medicine
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Cell Processing Facility At CiRA
Containing 8 Cell Processing Rooms
2F・Closed Cell Processing Room
2F・Passageway
1F・Inspection Room
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iPS cells from peripheral blood
QHJI (Most frequent HLA):Being distributed
RWMH(2nd most frequent ) :Being distributed
DRXT (3rd most frequent) :SCS production done(SCS; Secondary cell stock)
iPS cells from cord blood
YZWJ (Most frequent HLA) :Being distributed
ILCL (Most frequent) :SCS production done
GLKV (2nd most frequent) :SCS production done
iPS Cell Stock for Regenerative Medicine
As of Oct. 13, 2017, 19 donors identified,
which would cover ~50% of Japanese population.
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iPS Cell Stock for Regenerative Medicine
Clinical-grade iPSC
Distribution as of September 2017
11 projects in 8 institutions and companies
Sumitomo Dainippon Pharma Co., Ltd.
HEALIOS K.K.
Masayo Takahashi Lab (Riken)
Yonehiro Kanemura Lab (Osaka National Hospital)
Yoshiki Sawa Lab (Osaka Univ.)
Keiichi Fukuda Lab(Keio Univ.)Koji Eto, Jun Takahashi, Noriyuki Tsumaki Labs (CiRA), and so on
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iPS Cells
Conducted
by Kyoto Univ. & CiRA
Technology, iPS cells
provided by CiRA
Neurons
Neural stem cells
Heart Muscle
cells
Platelets
Retinal / Corneal
cells
Blood transfusion
Parkinson’s Disease
Immune cells
Cartilage Arthritic disorder
Pancreatic βcells
Regenerative Medicine Using iPS Cell Stock
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Clinical Research Using iPS Cell Stock
March 29, 201 Asahi Shimbun
HLA matching is useful!
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May 2017July 2016
“Match” or “Match if possible” increases by 6% from FY2016 to FY2017,
which accounts for 50% of the whole in FY2017.
SEND: 17 user research centers including 3 companies(Response rate 100%)
Questionnaire Survey for HLA Matching
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Hurdles
International Collaboration
Donor Recruitment
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Hurdles
International Collaboration
Donor Recruitment
Patent
Cost
Regulation
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Hurdles
International Collaboration
Donor Recruitment
Patent
Cost
Regulation
Each line: Different Product?
Regulation
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iPS Cell Stock Members
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Applications of iPS cells
Neurons
Skin cells
Blood cells
Regenerative
Medicine
Drug
Development
iPS cells
Muscle cellsHeart
Muscle cells
Cartilage
cells
Reprogramming
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・Bones formed in muscles, tendons and
ligaments
・80 patients in Japan
(700-1,000 patients worldwide)
Healthy person FOP patient
Fibrodysplasia Ossificans Progressiva (FOP)
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Associate Professor
Makoto Ikeya
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FOP patient-derived
iPS cells
Cartilage
Activin A
Elucidating Disease Mechanism
Hino et al., Journal of Clinical Investigation, 2017
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Drug Discovery using iPS cells
FOP cells+
Activin A
FOP cells+
Activin A+
Rapamycin
”Drug Repurposing”Hino et al., Journal of Clinical Investigation, 2017
FOP cells+
Activin A
Rapamycin
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August 2, 2017 Yomiuri Shimbun
The First Clinical Trial for FOP
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32
CiRA
Takeda
Collaboration with Takeda Pharmaceutical
(T-CiRA Program)
・20 billion yen over 10 years
・100 researchers
(each 50 from CiRA and Takeda)
・Accessible to Takeda’s chemical libraries
and expertise for drug developmentShonan Research Center
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Thank you for your attention!