Nerve growth factor improves survival and function of transplanted islets via TrkA-mediated β cell proliferation and revascularization

Background. Nerve growth factor (NGF), which plays important roles in promoting growth and differentiation of nerve cells, has recently been reported as a regulator in pancreatic β cells in terms of insulin releasing function. In this study, we examined whether NGF stimulation would promote islet graft survival and function in islet transplantation. Methods. We found that supplementation of cultured islets with NGF improved the viability of islet cells and induced the production of insulin, vascular endothelial growth factor, and cellular proliferative markers. Because a specific inhibitor of TrkA, K252a, blocked all these effects, we propose that the TrkA receptor is the mediator of NGF stimulation. Results. After transplantation to the kidney subcapsule and liver of syngenic diabetic mice, a higher rate of normoglycemic achievement, increased serum insulin, and improved glucose tolerance were observed in the mice transplanted with NGF-pretreated islet grafts. Histological analysis revealed higher expression of insulin and vascular endothelial growth factor, an increase in proliferative β cells, and revascularization in NGF-pretreated islet grafts without activation of any inflammatory cells. Conclusion.s The NGF treatment can therefore serve as a new and promising therapeutic tool for improving islet graft viability and function in islet transplantation.