In vitro preconditioning of insulin-producing cells with growth factors improves their survival and ability to release insulin

摘要

Glucose-induced oxidative stress in the diabetic pancreas directly affects viability and the consequent therapeutic outcome of transplanted stem cells. Pretreatment of stem cells with growth factors induces tolerance in them against various stresses (hypoxia, thermal or hyperglycaemic). This study investigated the effect of pretreatment on insulin-producing cells (IPCs) differentiated from adipose-derived mesenchymal stem cells (ADMSCs), with a combination of stromal cell-derived factor 1 alpha (SDF1 alpha) and basic fibroblast growth factor (bFGF) against hyperglycaemic stress (17 or 33 mM glucose). The results showed that IPCs pretreated with a combination of SDF1 alpha and bFGF exhibited maximally alleviated apoptosis, senescence and cell damage with a concomitantly increased release of insulin, enhanced cell proliferation and greater up-regulation of Insulin 1, Insulin 2, Ngn3, Pdx1 and Nkx6.2 when stressed with 33 mM glucose. These findings may offer an improved therapeutic outcome for the treatment of diabetes.