Basement Membrane Extract Preserves Islet Viability and Activity In Vitro by Up-Regulating α3 Integrin and Its Signal

Abstract

Survival of transplanted islets is limited partly because of the disruption of the islet basement membrane (BM) occurring during isolation. We hypothesized that the embedment of BM extract (BME) could induce a viable cell mass and prolong islet functionality before transplantation. A special reconstituted BME that solidifies into a gel at 37°C was used to embed isolated islets in this study. The strategy was used to re-establish the interaction between the islets and peri-islet BM. Islets embedded in BME showed lower caspase-3 levels and higher Akt activity than those in suspension. Moreover, we found for the first time that the expression of α3 integrin and focal adhesion kinase (FAK) and FAK activity was up-regulated in islets after BME embedment. The reverse effect was observed on islet apoptosis when islets rescued from a 24-hour suspension culture were embedded in BME for the next 24 hours. In addition, expression of pancreatic duodenal homeobox factor-1 and phospho-extracellular signal-regulated kinase 1/2 was partially preserved, suggesting the positive effect of BME on islet development. These results indicate that BME embedment of islets can up-regulate the expression of α3 integrin and its signal transduction, which may improve islet viability.