De novo formation of insulin-producing "neo-? cell islets" from intestinal crypts.

ABSTRACT: The ability to interconvert terminally differentiated cells could serve as a powerful tool for cell-based treatment of degenerative diseases, including diabetes mellitus. To determine which, if any, adult tissues are competent to activate an islet ? cell program, we performed an in vivo screen by expressing three ? cell "reprogramming factors" in a wide spectrum of tissues. We report that transient intestinal expression of these factors-Pdx1, MafA, and Ngn3 (PMN)-promotes rapid conversion of intestinal crypt cells into endocrine cells, which coalesce into "neoislets" below the crypt base. Neoislet cells express insulin and show ultrastructural features of ? cells. Importantly, intestinal neoislets are glucose-responsive and able to ameliorate hyperglycemia in diabetic mice. Moreover, PMN expression in human intestinal "organoids" stimulates the conversion of intestinal epithelial cells into ?-like cells. Our results thus demonstrate that the intestine is an accessible and abundant source of functional insulin-producing cells.

SUBMITTER: Chen YJ 

PROVIDER: S-EPMC4245054 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature