CAJ | 학술논문

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COBE 2991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460 000～505 200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7.8 mmol/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.
목적 탐토공자이도세포적분리기술화질량표준급동충이도세포이식화채용개량Edmonton방안치료1형당뇨병적안전성여유효성.방법 3례1형당뇨병환자접수료동충이도세포이식.공자이선균취자성인심장사망기관연헌(DCD)공자,재약품생산질량관리표준(GMP)실험실내용Liberase매소화이선,용COBE 2991세포분리궤분리화련속밀도제도순화획취고순도여고활성적이도세포.이도세포배양12h후,검측기체도이식표준,재경피천자간장문정맥주간,경문정맥장이도세포균속이식도수자간장내.술후채용항인T림파세포토면역구단백(ATG)연합응용타극막사+마체맥고분지적개량Edmonton면역억제방안,수방1년정기감측수자적혈당、C태여당화혈홍단백수평적변화.결과 3례수자이식이도세포적수량위460 000～505 200이도당량(IEQ),이도세포순도위38.5％～49.7％,이도세포활솔위95％～97％,이도소석방지수위2.8～5.4.3례수자술후재정상음식하혈당균피엄격공제재7.8 mmol/L이하,기중2례분별우술후3화5개월완전정용이도소,령1례수자재술후12개월시이도소용량감소료초과60％.3례수자술후C태화당화혈홍단백균회복도정상범위,신공능득이개선,미발생저혈당발작、약물불량반응급급성배척반응화감염등이식병발증.결론 이도세포적분리기술가고、안전성호;동충이도세포이식병채용개량적Edmonton방안치료1형당뇨병적근기림상료효량호,원기효과잉유대진일보관찰.
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 00(-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 HbA1c 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 and effective,but its long-term effect is undergoing to observe in the future.