Conversion of Human Gastric Epithelial Cells to Multipotent Endodermal Progenitors using Defined Small Molecules [array]

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. Human gastric epithelial cells (hGECs) and gastric subepithelial myofibroblasts (GSEMFs) are isolated from human stomach, and human duodenum epithelial cells (hDECs) are isolated from human duodenum. Human induced endodermal progenitor cells (hiEndoPCs) were reprogrammed from hGECs/hDECs by small molecules with the support of GSEMFs. Definitive endoderm cells (DEs) are derived from human embryonic stem cells by differentiation. Totally, 13 samples including two samples of hDECs, one sample of hGECs, two clones of D-hiEndoPCs, one clone of G-hiEndoPCs, four samples of DEs and three samples of GSEMFs were analyzed using microarray.