Stem cells in adult pancreas and their specific marker are poorly characterized. We hypothesized that pancreatic stem cells could evolve from the duct system in response to neogenic stimulation. Following partial pancreatectomy (Px), we found extensive formation of ductules consisting of nestin-positive epithelial cells with higher replicating ability in the neogenic foci after Px. The neogenic ductules were isolated for the culture of nestin-positive duct cells. These nestinpositive duct cells were numerous and displayed extensive self-replication in the duct cell explants, thus depicted as nestin-positive duct stem (NPDS) cells. Endocrine cells, mostly insulin cells were present in the explants at day 2 as single cells or as small clusters adjacent to the NPDS cells, and formed islet-like masses at day 3 of culture, implying islet cell differentiation from NPDS cells. We found transient up-regulation of PDX-1 expression by RT-PCR at day 3 after Px in pancreatic tissue. We investigated the effect of clusterin overexpression on differentiation of insulin beta cells 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 transfected cells. In conclusion, we suggest that NPDS cells could be generated from adult pancreas by neogenic motivations and they may differentiate into insulin-secreting-cells, and clusterin could stimulate not only differentiation of precursor cells in the pancreatic duct, but also proliferation of predifferentiated beta cells. Those differentiated beta cells are functional cells secreting insulin in response to glucose stimulation.
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