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

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.

iPS CellSkin cells

(induced Pluripotent Stem cell)

Human

2007

Mouse

2006

The Discovery of iPS Cells

Oct3/4 Sox2 Klf4 c-Myc

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

iPS Cells

Heart Muscle Cells

The Applications of iPS Cells

Neurons

Skin cells

Blood cells

Regenerative

Medicine

Drug

Development

iPS cells

Muscle cellsHeart

Muscle cells

Cartilage

cells

Reprogramming

Retinal Cells

World’s first Transplant in Human (2014)

Age-related Macular Degeneration

Dr. Masayo Takahashi

（RIKEN, CDB）(Photo by RIKEN)

iPS cells

Qualitycheck

Differentiatedcells

Qualitycheck

Sample

collection

Autologous iPS Cells

Autograft: Too expensive and time-consuming

iPS Cell Stock for Regenerative Medicine

Transplantation

HLA homozygous donor

HLA Homozygous “Super” Donors

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?

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?

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

Cell Processing Facility At CiRA

Containing ８ Cell Processing Rooms

2F・Closed Cell Processing Room

2F・Passageway

１F・Inspection Room

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.

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

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

Clinical Research Using iPS Cell Stock

March 29, 201 Asahi Shimbun

HLA matching is useful!

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

Hurdles

International Collaboration

Donor Recruitment

Hurdles

International Collaboration

Donor Recruitment

Patent

Cost

Regulation

Hurdles

International Collaboration

Donor Recruitment

Patent

Cost

Regulation

Each line: Different Product?

Regulation

iPS Cell Stock Members

Applications of iPS cells

Neurons

Skin cells

Blood cells

Regenerative

Medicine

Drug

Development

iPS cells

Muscle cellsHeart

Muscle cells

Cartilage

cells

Reprogramming

・Bones formed in muscles, tendons and

ligaments

・80 patients in Japan

(700-1,000 patients worldwide)

Healthy person FOP patient

Fibrodysplasia Ossificans Progressiva (FOP)

Associate Professor

Makoto Ikeya

FOP patient-derived

iPS cells

Cartilage

Activin A

Elucidating Disease Mechanism

Hino et al., Journal of Clinical Investigation, 2017

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

August 2, 2017 Yomiuri Shimbun

The First Clinical Trial for FOP

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

Thank you for your attention!