ISL-1 is induced in stomach mesenchyme in the presence of pancreatic epithelia

Background/Purposeβ-Cell replacement offers a potential cure for type 1 diabetes mellitus in children. We have previously shown that stomach mesenchyme (SM) is competent to derive islet tissue by mesenchymal-to-epithelial transition (iMET). The aim of this study was to further characterize the developmental fate of this SM in the presence of pancreatic epithelia (PE) in SM/PE recombinants. The homeobox ISL-1 was examined in these recombinants because this gene is restricted to the dorsal pancreatic mesenchyme and endocrine cells in early pancreatic development.MethodsChick-quail recombinants of SM + PE (n = 15) and whole stomach controls (n = 8) were cultured for 7 days. In addition, organ blocks were examined after normal development at days 4 to 10 (n = 4 for each stage). Tissues were analyzed using immunochemistry against quail-specific antigen and ISL-1.ResultsThirteen of 15 SM + PE recombinants expressed the ISL-1 protein in cells from SM origin. Nine of 15 of these recombinants showed iMET and coexpression of insulin, and ISL-1 was recorded.ConclusionsPancreatic epithelium is able to reprogram SM to a more caudal pancreatic fate when cocultured. Islet tissue by mesenchymal-to-epithelial transition observed in recombinants showed coexpression of insulin and ISL-1. These experiments are important to identify the molecular mechanisms behind iMET for potential therapeutic use for treating children with diabetes.