Research of the isolation of pancreatic stem / progenitor cells for the treatment of diabetes mellitus

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Success in islet transplantation-based therapies for type 1 diabetes mellitus and an extreme shortage of pancreatic islets has motivated efforts to develop renewable sources of islet-replacement tissue. Only a few attempts have been made at prospective isolation of pancreatic stem / progenitor cells, due to the lack of specific markers and the development of cell culture method. This study demonstrates the isolation of pancreatic stem / progenitor cells from the embryonic pancreas by cell sorting. Immunohistological study showed the two different cell surface markers are expressed in the epithelial cells and the surrounding mesenchymal cells, respectively. RT-PCR and microarray analysis demonstrated that pancreatic stem / progenitor cells are enriched in the specified cell population, with the combination of these surface markers. During in vivo differentiation, these cell populations have the ability for self-renewal and multipotency, including the formation of insulin-producing cells. Moreover, the islet-like cell clusters in the graft and the intracellular insulin C-peptide content in progenitor-derived cells were also observed to be comparable to that of the adult pancreatic islets. In addition, we obtained the differentiation of insulin-producing cells and glucagons-producing cells from these populations in vitro. Since the strategy is based on the cell sorting using cell surface markers common to human and rodents, it may promote strategies to drive transplantable islet-replacement tissues from human pancreatic stem / progenitor cells. Furthermore, we succeed in establishing the specified surface marker gene-knockout mice and start to analyze the interesting phenotype of these mice.