摘要
目的探讨供者胰岛细胞的分离技术和质量标准及同种胰岛细胞移植和采用改良Edmonton方案治疗1型糖尿病的安全性与有效性。方法3例1型糖尿病患者接受了同种胰岛细胞移植。供者胰腺均取自成人心脏死亡器官捐献（DCD）供者，在药品生产质量管理标准（GMP）实验室内用Liberase酶消化胰腺，用COBE2991细胞分离机分离和连续密度梯度纯化获取高纯度与高活性的胰岛细胞。胰岛细胞培养12h后，检测其达到移植标准，再经皮穿刺肝脏门静脉主干，经门静脉将胰岛细胞匀速移植到受者肝脏内。术后采用抗人T淋巴细胞兔免疫球蛋白（ATG）联合应用他克莫司＋吗替麦考酚酯的改良Edmonton免疫抑制方案，随访1年定期监测受者的血糖、C肽与糖化血红蛋白水平的变化。结果3例受者移植胰岛细胞的数量为460000~505200胰岛当量（IEQ），胰岛细胞纯度为38．5％～49．7％，胰岛细胞活率为95％～97％，胰岛素释放指数为2．8～5．4。3例受者术后在正常饮食下血糖均被严格控制在7．8mmol／L以下，其中2例分别于术后3和5个月完全停用胰岛素，另1例受者在术后12个月时胰岛素用量减少了超过60％。3例受者术后C肽和糖化血红蛋白均恢复到正常范围，肾功能得以改善，未发生低血糖发作、药物不良反应及急性排斥反应和感染等移植并发症。结论胰岛细胞的分离技术可靠、安全性好；同种胰岛细胞移植并采用改良的Edmonton方案治疗1型糖尿病的近期临床疗效良好，远期效果仍有待进一步观察。
Objective To investigate the pancreatic islet cell isolation technology, quality standards, and safety and effectiveness of allograft islet cell transplantation and modified Edmonton protocol in the treatment of type 1 diabetes （T1DM）. Method Three cases of T1DM received allograft islet cell transplantation. The pancreas was taken from adult organ donation after cardiac death donor. All pancreatic organs were digested by Liberase enzyme, COBE 2991 cell separator, and discontinuous density gradient purification, to obtain high purity and high activity of islet cells. All these procedures were conducted in our GMP facilities. After culture for 12 h, testing islets reached transplant standards. After the percutaneous puncture of hepatic portal vein trunk of the recipients, islet cells were transplanted evenly through the portal vein into the liver of recipients. After islet cell transplantation, a modified Edmonton immunosuppressive protocol containing antithymocyte globulin （ATG）, tacrolimus and mycophenolate mofetil was used, and the changes in blood glucose, C peptide and glycate hemoglobin were monitored regularly during a follow-up period of one year. Result The transplanted islet cells of 3 recipients were 460 000-505 200 IEQ, and islet purity and viability were 38.5±49. 7% and 95%-97% respectively. The stimulation index of human islet was 2. 8-5.4. The glucose levels of 3 recipients in the normal diet were strictly controlled below 7.8 mmol/L. Two recipients remained insulin-independent after 3-5 months. The dosage of insulin was decreased by 60% in 1 patient after 12 months. The levels of C-peptide and HbAlc were all within normal range and renal functions were improved. No complications related to islet infusion including hypoglycemia, adverse drug reactions, acute rejection and infection were observed. Conclusion Our isolation techniques and methods of islet cells are reliable. Allograft islet cell transplantation and the improved Edmonton protocol in the short-term for treatment of T1DM is safe a
出处
《中华器官移植杂志》
CAS
CSCD
北大核心
2014年第3期160-164,共5页
Chinese Journal of Organ Transplantation
基金
四川省卫生厅课题基金（100489）
四川省科技厅科技支撑计划课题基金（2010FZ0098）
四川省科技厅国际合作计划课题基金（2011HH0022）
关键词
胰岛细胞移植
糖尿病
1型
免疫抑制法
Pancreatic islet cells transplantation
Diabetes mellitus type 1
Irnmunosuppression
