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Nerve Growth Factor Improves Survival and Function of Transplanted Islets Via TrkA-mediated β Cell Proliferation and
Tatsuo Hata1, Naoaki Sakata, Gumpei Yoshimatsu
11 Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan. 2 Division of Integrated Surgery and Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan. 3 Division of International Cooperation for Disaster Medicine, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
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.
Conclusions:
The NGF treatment can therefore serve as a new and promising therapeutic tool for improving islet graft viability and function in islet transplantation.
