Embryonic Stem Cell Transplantation Correlates With Endogenous Neurogenin 3 Expression and Pancreas Regeneration in Streptozotocin-injured Mice

作者：Kodama Maho; Tsukamoto Katsura; Yoshida Kimiko; Aoki Kazunori; Kanegasaki Shiro; Quinn Gary^*

来源：Journal of Histochemistry and Cytochemistry, 2009, 57(12): 1149-1158.

DOI：10.1369/jhc.2009.954206

• pancreas regeneration
• diabetes
• neurogenin 3
• PDX-1
• pancreatic islets
• embryonic stem cells
• streptozotocin
• islet
• pancreatic beta cells
• cell transplantation

Pancreatic beta cell regeneration remains poorly understood, yet stimulation of adult beta cell neogenesis could lead to therapies for type 1 and type 2 diabetes. We studied the effect of embryonic stem (ES) cell transplantation on pancreas regeneration following beta cell injury. Female Balb/c nude mice were treated with streptozotocin to induce hyperglycemia and received an ES cell transplant 24 hr later beneath the renal capsule. Transplantation of ES cells prevented hyperglycemia in a subset of mice, maintaining euglycemia and mild glucose tolerance up to 5 weeks. Pancreata of euglycemic mice showed histological evidence of beta cell regeneration and expression of pancreas and duodenum transcription factor-1 (PDX-1) and neurogenin 3 (Ngn3) in ductal epithelium. Cell tracing analysis indicated that significant beta cell neogenesis from progenitor cells occurred between 2 to 3 weeks following injury in ES cell-transplanted mice but not in sham-transplanted animals. Significantly, whereas pancreas-localized ES cells or their derivatives were adjacent to sites of regeneration, neogenic pancreatic epithelia, including Ngn3( ) cells, were endogenous. in conclusion, transplanted ES cells can migrate to the injured pancreas. Transplantation is associated with enhanced endogenous regeneration characterized by expression of Ngn3 and increased beta cell differentiation from endogenous progenitor cells. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. (J Histochem Cytochem 57:1149-1158, 2009)

• 出版日期2009-12