Hepatic differentiation and transplantation of induced pluripotent stem cells

2015/08/23

Stem cells

induced pluripotent stem (iPS) cells

2006MEF

MOUSE

iPS cell culture

iPS cell differentiation

Patient-pecific iPS cells

Hemophilia B

iPS cells hepatocytes

In vitro

• hepatic differentiation

In vivo

• function

Fetal liver development

Behbahan, I. S., Y. Duan, et al. (2011). Stem Cell Rev

Human Embryonic Stem Cells Differentiate Toward Hepatocytes

Differentiation of iPSCs Toward Hepatocytes

iPS cells hepatocytes

Si-Tayeb, K., F. K. Noto, et al. (2010). Hepatology

Differentiation of hepatocytes from human iPS cells

Integration of hiPS cell-derived hepatocytes into the mouse hepatic parenchyma

3x105 cells7 days

right lateral liver lobe

Albumin

Efficient hepatic differentiation of human iPS cells

Song, Z., J. Cai, et al. (2009). Cell Res

Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells

3 d

7 d

80% 50-60%

60% 60%

Differentiation of hES toward a hepatocyte phenotype

Basma, H., A. Soto-Gutierrez, et al. (2009). Gastroenterology

Stage 1 Stage 2 Stage 3

Day -2 Day 0 Day 3 Day 11 Day 14

EBs Activin AbFGF

HGFDMSO

DEX +ASGPR

Day 18

Characterization of hepatocyte-directed cells

55% 12%

Characterization and transplantation of ES-derived cells

Comparison of directed hepatic differentiation in vitro among iPSC lines

Liu, H., Y. Kim, et al. (2011). Sci Transl Med

In vivo engraftment and regeneration potential of hepatic cells derived from human iPSCs and ESCs

In vivo engraftment efficiency of human iPSC-derived multistage hepatic cells

Thank you!