Generation of Insulin Expressing Cells in Mouse Small Intestine by Pdx1, MafA, and BETA2/NeuroD

Abstract

To develop the beta-like cells for diabetes therapy, adult stem cells have been identified in various tissues and studied for their conversion into beta cells. Pancreatic progenitor cells are derived from the endodermal epithelium and formed in a similar manner as gut progenitor cells. Here, we generated insulin-expressing cells from the intestinal epithelial cells that induced many of the specific pancreatic transcription factors using adenoviral vectors carrying three genes: Pdx1, MafA, and BETA2/NeuroD (PMB). By direct injection into the whole intestine, adenoviruses (Ad) were successfully delivered to the intestine. After virus injection, we could confirm that the small intestine of the mouse was appropriately overexpressed with the Ad-Pdx1 and triple Ad-PMB. Four weeks after the injection, insulin mRNA was expressed in the small intestine, and the insulin gene expression was induced in Ad-Pdx1 as well as Ad-PMB compared to control Ad-GFP. In addition, the conversion of intestinal cells into insulin-expressing cells was detected in parts of the crypts and villi located in the small intestine. In conclusion, these data indicated that Pdx1, MafA, and BETA2/NeuroD facilitate the differentiation of mouse intestinal cells into insulin-expressing cells. The small intestine is an accessible and abundant source of surrogate insulin-producing cells. Disclosure L. So Hyun: None. J. Kim: None. K. Yoon: None.