In Vitro Expansion And Characterization Of Mouse Fetal Pancreatic Progenitor Cells

There is a world-wide epidemic of diabetes mellitus. The total number of people with diabetes is estimated to be about 150 million,including approximately 30 million in China. Furthermore, the incidence of diabetes increased dramatically in recent years. The success of islet transplantation by the Edmonton's group stimulates new hope to the diabetic patients. However, the lack of transplantable human islets greatly limits the application of this technology. In this study, mice were used as the animal model to establish a novel co-culture system for the generation of pancreatic stem cells. To achieve this, pancreatic cells isolated from embryos of day 13.5-18.5 were cultured with a feeder cell layer op9-DL1, which expressed constitutively the Notch1 ligand DL1. Thus, Notch1 signaling pathway suppressed the differentiation of pancreatic stem cells while still allowing the proliferation to occur. The results demonstrated that fetal pancreatic stem cells could be expanded in the co-culture system. Furthermore, these fetal pancreatic stem cells had a unique cobble-stone morphology. Consistent with the inhibitory signaling from Notch1, fetal pancreatic stem cells expressed PDX-1, but not proinsulin-2 and neurogenin3 (ngn3). More importantly, fetal pancreatic stem cells were induced to form islet-like aggregates when cultured on films made of polyesters poly(3-hydroxybutyrate-co -3-hydroxyhexanoate) (PHBHHx). Therefore, our study is not only important theoretically, but may also contribute significantly to the treatment of diabetes.