Cell Stem Cell. 2016 Jul 19. pii: S1934-5909(16)30156-4. doi: 10.1016/j.stem.2016.06.006. [Epub ahead of print]

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

Wang Y¹, Qin J², Wang S³, Zhang W⁴, Duan J⁵, Zhang J⁵, Wang X⁶, Yan F⁴, Chang M⁴, Liu X⁷, Feng B⁸, Liu J⁵, Pei X⁹.

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.