Differentiation of islet cells in long-term culture

Our previous studies in the hamster pancreatic cancer model have shown that exocrine pancreatic cancer arises from ductal/ductular cells, as well as f rom within the islets, most probably from islet precursor (stem) cells. To identify and characterize these cells, we established a long-term culture f rom isolated hamster islets and investigated their growth, differentiation, and expression of biomarkers. Islets maintained their original form and st ructure within the first 14 days in culture. However, beginning at day 7, d uctular structures began to form within the islets. At day 21 in culture, a cinar cells, intermediary cells, oncocytes, and cells comparable to pancrea tic hepatocytes also appeared between ductular and endocrine cells. The num ber of duct-like cells gradually increased, whereas the number of hormone-p roducing cells decreased. After 35 days in culture, the exocrine cells disa ppeared, and undifferentiated cells formed a monolayer. These cells express ed cytokeratins, alpha(1)-antitrypsin, transforming growth factor-alpha, ep idermal growth factor receptor, carbonic anhydrase II, vimentin, laminin, a nd showed binding to tomato lectin and Phaseolus vulgaris leukoagglutinin. They did not express the regulatory transcriptional factors, insulin-promot ing factor 1, NKx6.1, Paw6, and NeuroD. The results thus indicate that isle t cells have potential to form exocrine cells. At present, it is not clear whether these cells originate from preexisting stem cells or from transdiff erentiated islet cells.