BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeuti...BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeutic method due to its ability to promote the regeneration of pancreaticβcells.However,current studies have focused on its efficacy,and there are few clinical studies on its safety.AIM To evaluate the safety of human umbilical cord(hUC)-MSC infusion in T2DM treatment.METHODS An open-label and randomized phase 2 clinical trial was designed to evaluate the safety of hUC-MSC transplantation in T2DM in a Class A hospital.Ten patients in the placebo group received acellular saline intravenously once per week for 3 wk.Twenty-four patients in the hUC-MSC group received hUC-MSCs(1×106 cells/kg)intravenously once per week for 3 wk.Diabetic clinical symptoms and signs,laboratory findings,and imaging findings were evaluated weekly for the 1st mo and then at weeks 12 and 24 post-treatment.RESULTS No serious adverse events were observed during the 24-wk follow-up.Four patients(16.7%)in the hUC-MSC group experienced transient fever,which occurred within 24 h after the second or third infusion;this did not occur in any patients in the placebo group.One patient from the hUC-MSC group experienced hypoglycemic attacks within 1 mo after transplantation.Significantly lower lymphocyte levels(weeks 2 and 3)and thrombin coagulation time(week 2)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).Significantly higher platelet levels(week 3),immunoglobulin levels(weeks 1,2,3,and 4),fibrinogen levels(weeks 2 and 3),D-dimer levels(weeks 1,2,3,4,12,and 24),and neutrophil-to-lymphocyte ratios(weeks 2 and 3)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).There were no significant differences between the two groups for tumor markers(alpha-fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 199)or blood fat.No liver damage or other side effects were observed on chest X-ray.CONCLUSION Our study suggested that hUC-MSC transplantation has good tolerance and high safety in the treatment of T2DM.It can improve human immunity and inhibit lymphocytes.Coagulation function should be monitored vigilantly for abnormalities.展开更多
基金Shenzhen Science and Technology Innovation Committee Projects,No.JCYJ20170816105416349Shenzhen High-Level Hospital Construction Fund,Shenzhen Key Medical Discipline Construction Fund,No.SZXK010.
文摘BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeutic method due to its ability to promote the regeneration of pancreaticβcells.However,current studies have focused on its efficacy,and there are few clinical studies on its safety.AIM To evaluate the safety of human umbilical cord(hUC)-MSC infusion in T2DM treatment.METHODS An open-label and randomized phase 2 clinical trial was designed to evaluate the safety of hUC-MSC transplantation in T2DM in a Class A hospital.Ten patients in the placebo group received acellular saline intravenously once per week for 3 wk.Twenty-four patients in the hUC-MSC group received hUC-MSCs(1×106 cells/kg)intravenously once per week for 3 wk.Diabetic clinical symptoms and signs,laboratory findings,and imaging findings were evaluated weekly for the 1st mo and then at weeks 12 and 24 post-treatment.RESULTS No serious adverse events were observed during the 24-wk follow-up.Four patients(16.7%)in the hUC-MSC group experienced transient fever,which occurred within 24 h after the second or third infusion;this did not occur in any patients in the placebo group.One patient from the hUC-MSC group experienced hypoglycemic attacks within 1 mo after transplantation.Significantly lower lymphocyte levels(weeks 2 and 3)and thrombin coagulation time(week 2)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).Significantly higher platelet levels(week 3),immunoglobulin levels(weeks 1,2,3,and 4),fibrinogen levels(weeks 2 and 3),D-dimer levels(weeks 1,2,3,4,12,and 24),and neutrophil-to-lymphocyte ratios(weeks 2 and 3)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).There were no significant differences between the two groups for tumor markers(alpha-fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 199)or blood fat.No liver damage or other side effects were observed on chest X-ray.CONCLUSION Our study suggested that hUC-MSC transplantation has good tolerance and high safety in the treatment of T2DM.It can improve human immunity and inhibit lymphocytes.Coagulation function should be monitored vigilantly for abnormalities.
文摘目的探讨自体骨髓干细胞(bone marrow stem cells,BMSCs)经胰背动脉移植治疗2型糖尿病(type 2 diabe-tes mellitus,T2DM)的有效性及安全性。方法回顾性分析2009年6月至2011年4月在我科住院符合纳入标准的6例2型糖尿病患者(3男3女),年龄(45.67±14.92)岁,实施自体骨髓干细胞移植。①动员骨髓;②采集骨髓;③分离骨髓干细胞;④将骨髓干细胞注入胰背动脉;⑤观察移植前后血糖、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、胰岛功能、C肽曲线下面积(area under curve for C-peptide,AUCC)及胰岛素用量等变化,记录治疗过程中及治疗后的不良反应;对干细胞移植的安全性及疗效进行评估。结果移植前后:①糖化血红蛋白由(10.33±2.78)%降至(7.05±0.90)%,有2例患者的糖化血红蛋白<7%;②空腹C肽(fasting C-peptide,FC-P)由(0.71±0.54)ng/ml升至(1.54±0.63)ng/ml(P<0.05),餐后2 h C肽(2 h postprandial C-peptide,2 h C-P)由(1.63±0.88)ng/ml升至(4.67±2.31)ng/ml(P<0.05),C肽曲线下面积由(2.29±1.31)ng/ml增至(6.05±2.94)ng/ml(P<0.05);③胰岛素用量由(27.17±13.08)U/d降到(18.63±7.04)U/d,其中2位患者停用皮下注射胰岛素改为口服药物降糖治疗;④自体骨髓干细胞移植过程中及术后随访均未观察到不良反应,移植前后肿瘤标志物及血淀粉酶均正常。结论自体骨髓来源干细胞移植可改善2型糖尿病患者的胰岛功能,减轻其对外源性降糖药物的依赖,且安全性可行。
