고려대학교

초록/요약

Stem cells in adult pancreas and their specific marker are poorly characterized. We hypothesized that pancreatic stemcells could evolve from the duct system in response to neogenic stimulation. Following partial pancreatectomy (Px), wefound extensive formation of ductules consisting of nestin-positive epithelial cells with higher replicating ability in theneogenic foci after Px. The neogenic ductules were isolated for the culture of nestin-positive duct cells. These nestinpositiveduct cells were numerous and displayed extensive self-replication in the duct cell explants, thus depicted asnestin-positive duct stem (NPDS) cells. Endocrine cells, mostly insulin cells were present in the explants at day 2 assingle cells or as small clusters adjacent to the NPDS cells, and formed islet-like masses at day 3 of culture, implyingislet cell differentiation from NPDS cells. We found transient up-regulation of PDX-1 expression by RT-PCR at day 3after Px in pancreatic tissue. We investigated the effect of clusterin overexpression on differentiation of insulin betacells from duct cells We found that the number of insulin producing cells increased 11.5 fold when clusterin was overexpressed.Insulin expression, both insulin mRNA and peptide levels, was increased in clusterin cDNA transfectedcells.In conclusion, we suggest that NPDS cells could be generated from adult pancreas by neogenic motivations and theymay differentiate into insulin-secreting-cells, and clusterin could stimulate not only differentiation of precursor cells inthe pancreatic duct, but also proliferation of predifferentiated beta cells. Those differentiated beta cells are functionalcells secreting insulin in response to glucose stimulation.