人脐带间充质干细胞治疗1型糖尿病的远期疗效观察

Long-term effects of the implantation of human umbilical cord-derived mesenchymal stem cells for type 1 diabetes mellitus

目的探讨人脐带间充质干细胞(HUC-MSCs)移植治疗1型糖尿病的远期疗效。方法收集2009年9月至2011年12月芜湖市第二人民医院内分泌科收治住院行HUC-MSCs移植治疗的15例1型糖尿病患者的临床资料,包括移植前及移植后10年时空腹血糖、HbA1C、平均血糖波动幅度(MAGE)、空腹C肽、胰岛素使用剂量及谷氨酸脱羧酶抗体(GADA)。结果移植后,发现1例患者(6.67%)合并肿瘤(乳腺癌),所有1型糖尿病患者均在1周后因低血糖频发而出现日胰岛素总量减少,半年后有4例(26.67%)停用胰岛素治疗,其中1例(6.67%)至今未使用胰岛素且GADA转阴,剩余3例(20.00%)均在移植后3~5年内再次使用胰岛素,但是日胰岛素总量较移植前显著减少[(18.00±1.00)U对(29.00±1.73)U,P<0.01]。未停用胰岛素的11例(73.33%)患者日胰岛素总量亦较移植前显著减少[(18.09±0.83)U对(29.64±0.89)U,P<0.01]。所有患者移植后的MAGE较移植前明显减少[(6.14±0.25)mmol/L对(9.72±0.32)mmol/L,P<0.01],空腹C肽水平较移植前明显改善[(0.91±0.03)nmol/L对(0.11±0.01)nmol/L,P<0.01]。而移植前后空腹血糖、HbA1C无明显差异。结论HUC-MSCs能更好地恢复胰岛细胞分泌功能,减少胰岛素用量,减少血糖波动,对1型糖尿病可能具有远期疗效,虽然具体机制尚不清楚,但有望成为治疗1型糖尿病的一种有效策略。

Objective To investigate the long-term effect of the implantation of human umbilical cord-derived mesenchymal stem cells(HUC-MSCs)for type 1 diabetes mellitus.Methods Fifteen patients with type 1 diabetes mellitus were treated with HUC-MSCs from September 2009 to December 2011 at Department of Endocrinology and Metabolism,the Second People′s Hospital.Patients were followed-up for 10 years and the parameters were collected including fasting blood glucose,HbA1C,mean amplitude of glycemic excursions(MAGE),fasting C-peptide,daily insulin doses and glutamic acid decarboxylase antibody(GADA).Results Among 15 patients,1 patient(6.67%)was found with breast cancer.All patients with type 1 diabetes mellitus decreased daily insulin doses due to frequent hypoglycemia one week later.Six months later,4 patients(26.67%)stopped insulin injection.While among the 4 patients,1 patient(6.67%)had not yet used insulin until today and GADA was negative,the other 3 patients(20.00%)restarted insulin within 3-5 years after implantation with significantly less daily insulin doses[(18.00±1.00)U vs(29.00±1.73)U,P<0.01].The remaining 11 patients(73.33%)with type 1 diabetes mellitus who did not stop insulin also had significantly lower daily insulin doses[(18.09±0.83)U vs(29.64±0.89)U,P<0.01].The level of MAGE was signicantly decreased compared to those of pre-implantation[(6.14±0.25)mmol/L vs(9.72±0.32)mmol/L,P<0.01],while fasting C-peptide level was significantly improved[(0.91±0.03)nmol/L vs(0.11±0.01)nmol/L,P<0.01].There were no significant differences in fasting blood glucose and HbA1C before and after implantation.Conclusions The implantation of HUC-MSCs for the treatment of type 1 diabetes mellitus can restore the function of isletβcells,decrease daily insulin doses and reduce blood glucose fluctuations in the long term.Although precise mechanisms are unknown,this therapy is expected to be an effective strategy for treatment of type 1 diabetes mellitus.