Beneficial effects of nerve growth factor on islet transplantation

Abstract

Objective: Development of the Edmonton protocol was a pivotal contribution to clinical islet transplantation (ITx). Persistent limitations to ITx include insufficient supply and posttransplant functional failure of islets. In this study, nerve growth factor (NGF) was used to enhance both cultured and transplanted beta-cell function, thus achieving prolonged graft survival.

Methods: Fluorescence microscopy with ethidium bromide and SYTO green staining was used to evaluate balb/c mouse islet viability. Islets were syngeneically transplanted under the kidney capsule of recipients with streptozotocin-induced diabetes. Intraperitoneal glucose tolerance was used to test posttransplant function.

Results: Improved viability was found in murine islets cultured for 48 hours in 500 ng/mL NGF (P < .05). A submarginal islet mass (260 islet equivalents/recipient) was used for ITx. The NGF-culture resulted in prolonged islet survival (24.7 days vs 5.5 days without NFG culture, n = 6). Intravenous injection of NGF (6 mug) on the day of transplant and postoperative days (POD) 1 + 2 prolonged islet survival from 4.1 days (no treatment) to 13.2 days (n = 6). Glucose tolerance testing performed at posttransplant day 4 showed improvement at 60 and 120 minutes in recipients treated intravenously with NGF (blood glucose of 95 +/- 15 vs 210 +/- 78 and 57 +/- 6 vs 176 +/- 70 mg/dL, respectively).

Conclusion: NGF may improve beta-cell function and result in prolonged survival of both cultured and transplanted islets.