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The transplantation of pancreatic tissue has been anticipated to serve as a radical treatment for diabetes mellitus. However, the identification of the stem cells, and elucidation of their differential lineage and controlling mechanisms are prerequisites to ensure effective transplantation. We conducted an immunohistochemical study to determine the proliferation and differentiation dynamics of pancreatic endocrine cells in the rat pancreas 1 to 28 days after a 90% pancreatectomy. Regeneration of endocrine cells started immediately after pancreatectomy. The process of regeneration included the proliferation of preexisting islet cells and neogenesis of endocrine cells from epithelial cells of the most peripheral duct. Intercalated ductal cells and centroacinar cells were speculated to be the major sources of neogenesis, from which islet tissue was formed. Glucagon cells were the first endocrine cells differentiated, some of which transformed to insulin cells by a mechanism of non-replication. These results indicate that endocrine stem cells exist among the intercalated ductal and/or centroacinar cells, and these special regions should be utilized in transplantation for the successful treatment of diabetes.

Differentiation and proliferation of endocrine cells in the regenerating rat pancreas after 90% pancreatectomy