Miao G, Mace J, Kirby M, Hopper A, Peverini R, Chinnock R, Shapiro J, Hathout E
Department of Pediatrics, Loma Linda University, 11175 Campus Street, Loma Linda, CA 92354, USA.
Transplant Proc. 2005 Oct;37(8):3490-2. doi: 10.1016/j.transproceed.2005.09.057.
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.
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.
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).
NGF may improve beta-cell function and result in prolonged survival of both cultured and transplanted islets.
埃德蒙顿方案的制定对临床胰岛移植（ITx）具有关键贡献。ITx持续存在的局限性包括胰岛供应不足和移植后功能衰竭。在本研究中，使用神经生长因子（NGF）来增强培养和移植的β细胞功能，从而实现延长移植物存活时间。
采用溴化乙锭和SYTO绿色染色的荧光显微镜评估Balb/c小鼠胰岛活力。将胰岛同基因移植到链脲佐菌素诱导糖尿病的受体肾被膜下。采用腹腔内葡萄糖耐量试验来测试移植后功能。
在500 ng/mL NGF中培养48小时的小鼠胰岛活力得到改善（P <.05）。使用亚临界胰岛量（260个胰岛当量/受体）进行ITx。NGF培养导致胰岛存活时间延长（24.7天对未用NGF培养的5.5天，n = 6）。移植当天及术后第1天和第2天静脉注射NGF（6μg）使胰岛存活时间从4.1天（未治疗）延长至13.2天（n = 6）。移植后第4天进行的葡萄糖耐量试验显示，静脉注射NGF治疗的受体在60分钟和120分钟时血糖有所改善（血糖分别为95±15对210±78以及57±6对176±70 mg/dL）。
NGF可能改善β细胞功能，并导致培养和移植的胰岛存活时间延长。
