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Cell Stem Cell. 2016 Oct 6;19(4):449-461. doi: 10.1016/j.stem.2016.06.006. Epub 2016 Jul 21.

Conversion of Human Gastric Epithelial Cells to Multipotent Endodermal Progenitors using Defined Small Molecules.

Author information

1
Tissue Engineering Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China. Electronic address: wangyf1972@gmail.com.
2
Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China; South China Research Center for Stem Cell and Regenerative Medicine, South China Institute of Biomedicine, Guangzhou 510005, China.
3
Tissue Engineering Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China; Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China; South China Research Center for Stem Cell and Regenerative Medicine, South China Institute of Biomedicine, Guangzhou 510005, China.
4
Tissue Engineering Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
5
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
6
Key Laboratory of National Education, Ministry for Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Huhhot 010000, China; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
7
Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
8
Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
9
Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China; South China Research Center for Stem Cell and Regenerative Medicine, South China Institute of Biomedicine, Guangzhou 510005, China. Electronic address: peixt@nic.bmi.ac.cn.

Abstract

Endodermal stem/progenitor cells have diverse potential applications in research and regenerative medicine, so a readily available source could have widespread uses. Here we describe derivation of human induced endodermal progenitor cells (hiEndoPCs) from gastrointestinal epithelial cells using a cocktail of defined small molecules along with support from tissue-specific mesenchymal feeders. The hiEndoPCs show clonal expansion in culture and give rise to hepatocytes, pancreatic endocrine cells, and intestinal epithelial cells when treated with defined soluble molecules directing differentiation. The hiEndoPC-derived hepatocytes are able to rescue liver failure in Fah-/-Rag2-/- mice after transplantation, and, unlike hESCs, transplanted hiEndoPCs do not give rise to teratomas. Since human gastric epithelial cells are readily available from donors of many ages, this conversion strategy can generate clonally expandable cell populations with a variety of potential applications, including personalized drug screening and therapeutic strategies for liver failure and diabetes.

PMID:
27452176
DOI:
10.1016/j.stem.2016.06.006
[Indexed for MEDLINE]
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