Research Description:

De-Differentiation Of Human/Mouse Mature Exocrine Pancreatic Cells and Type 1 Diabetes

There is a poorly understood approach for potentially deriving beta cells or islets. This phenomenon is termed “de-differentiation”. The extent and feasibility of this process remains unknown. In essence, de-differentiation defines processes that redirect a set of mature cells to switch-off current functions and assume a progenitor phenotype that can be then turned on to initiate a new genetic program to give rise to a distinctly different type of mature cells. A phenotypic freezing at the stage of “switching-off current functions and turning-on new functions would result in ‘progenitor’ type cells (as indicated above) that may be expanded in-vitro as long-term cultures. Of interest, some have suggested that most of the adult pancreatic stem cells could just be de-differentiated cells that respond to environmental demands to produce new cell types. Further, the pancreatic exocrine compartment (acinar and ductal cells) has been shown, in-vitro, to have propensity to digress into endocrine differentiation pathway. However, the extent of the feasibility, frequency and stability of in-vitro de-differentiation of exocrine cells remain unknown. It should be emphasized that >95% of pancreatic cells following islet isolation (in transplant centers) is considered “junk” and hence discarded. Our de-differentiation studies will utilize this discarded material to generate insulin-producing cells and explore the possibility of utilizing them for implantation.