derivation and characterization of hepatic progenitor cells from human embryonic stem cells推导和描述来自人类胚胎干细胞的肝祖细胞.pdfVIP

Derivation and Characterization of Hepatic Progenitor Cells from Human Embryonic Stem Cells 1 1 1 1,2 1,2 1 1,2 1,2 Dongxin Zhao , Song Chen , Jun Cai , Yushan Guo , Zhihua Song , Jie Che , Chun Liu , Chen Wu , Mingxiao Ding1, Hongkui Deng1,2* 1 Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, China, 2 Laboratory of Chemical Genomics, Shenzhen Graduate School of Peking University, The University Town, Shenzhen, China Abstract The derivation of hepatic progenitor cells from human embryonic stem (hES) cells is of value both in the study of early human liver organogenesis and in the creation of an unlimited source of donor cells for hepatocyte transplantation therapy. Here, we report for the first time the generation of hepatic progenitor cells derived from hES cells. Hepatic endoderm cells were generated by activating FGF and BMP pathways and were then purified by fluorescence activated cell sorting using a newly identified surface marker, N-cadherin. After co-culture with STO feeder cells, these purified hepatic endoderm cells yielded hepatic progenitor colonies, which possessed the proliferation potential to be cultured for an extended period of more than 100 days. With extensive expansion, they co-expressed the hepatic marker AFP and the biliary lineage marker KRT7 and maintained bipotential differentiation capacity. They were able to differentiate into hepatocyte-like cells, which expressed ALB and AAT, and into cholangiocyte-like cells, which formed duct-like cyst structures, expressed KRT19 and KRT7, and acquired epithelial polarity. In conclusion, this is the first