Small molecules facilitate the reprogramming of mouse fibroblasts into pancreatic lineages.

ABSTRACT: Pancreatic ? cells are of great interest for the treatment of type 1 diabetes. A number of strategies already exist for the generation of ? cells, but a general approach for reprogramming nonendodermal cells into ? cells could provide an attractive alternative in a variety of contexts. Here, we describe a stepwise method in which pluripotency reprogramming factors were transiently expressed in fibroblasts in conjunction with a unique combination of soluble molecules to generate definitive endoderm-like cells that did not pass through a pluripotent state. These endoderm-like cells were then directed toward pancreatic lineages using further combinations of small molecules in vitro. The resulting pancreatic progenitor-like cells could mature into cells of all three pancreatic lineages in vivo, including functional, insulin-secreting ?-like cells that help to ameliorate hyperglycemia. Our findings may therefore provide a useful approach for generating large numbers of functional ? cells for disease modeling and, ultimately, cell-based therapy.

SUBMITTER: Li K 

PROVIDER: S-EPMC4747235 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature