Adult Pancreatic Progenitor Cells

Diana L. Clarke

Diabetes Research Division, ES Cell International
Cambridge, MA

Adult pancreatic progenitor cells hold potential promise as a cell source for replacement cell therapy and in expanding our understanding of endogenous progenitor cell recruitment and differentiation. Previous methods describing the culture and differentiation of pancreatic progenitor cells into cells derived from the endocrine lineage have yielded promising but inefficient results. In order for therapeutic methods employing stem or progenitor cells to become a reasonable treatment option for a variety of diseases such as diabetes, there exists a need for improved methods for purifying, expanding and differentiating such cells. We have developed an efficient multi-step culture method to differentiate pancreatic progenitor cells from purified adult pancreatic ducts into glucose responsive islet-like structures that can restore normoglycemia in streptozotocin (STZ) induced diabetic NOD-SCID mice. We have used this culture method as a model system to understand the progressive differentiation of adult duct progenitor cells into mature functional beta cells and to search for a progenitor cell population that can be expanded significantly in culture. Analyses of the differentiating progenitor cell populations in this model have shown that these cells follow a determination and differentiation program very similar to the developing embryonic pancreatic endoderm. Additionally, factors found to be expressed during regeneration of the adult pancreas increase proliferation of a specific subset of adult islet progenitor cells present in these cultures.