Preservation of islet survival by upregulating α3 integrin signaling: the importance of 3-dimensional islet culture in basement membrane extract.

AIM

Islet transplantation is a promising treatment to cure diabetes, but is associated with a high rate of early graft failure. The isolation process leads to the loss of the surrounding extracellular matrix, resulting in eventual islet disintegration and apoptosis. The purpose of this study was to determine the effects on the viability of isolated islets of embedding islets in reconstituted basement membrane extract (BME), which is similar to the normal peri-islet BM composition in vivo.

METHODS

Isolated mouse islets were embedded in BME gel for 24 or 48 hours. Expression of caspase-3, α3, and α5, focal adhesion kinase (FAK), phosphor-FAK, and pancreatic duodenal homeobox factor (PDX)-1 were detected with Western immunoblotting.

RESULTS

Impaired aggregation of single islet cells could only be observed in non-BME medium. Islets embedded in BME gel were partially protected from anoikis showed decreased caspase-3 compared with non-BME islets. We also observed an increase of α3 integrin, FAK protein level, and FAK activity. Furthermore, expression of PDX-1 was preserved at 48 hours, suggesting a positive contribution of BME to β-cell activity.

CONCLUSION

These results indicated that embedding islets in BME can upregulate α3 integrin, which may result in preservation of viability and function of isolated islets.