Islet cell transplantation has therapeutic potential to treat type 1 diabetes,which is characterized by autoimmune destruction of insulin-producing pancreatic isletβcells.It represents a minimal invasive approach for...Islet cell transplantation has therapeutic potential to treat type 1 diabetes,which is characterized by autoimmune destruction of insulin-producing pancreatic isletβcells.It represents a minimal invasive approach forβcell replacement,but long-term blood control is still largely unachievable.This phenomenon can be attributed to the lack of islet vasculature and hypoxic environment in the immediate post-transplantation period that contributes to the acute loss of islets by ischemia.Moreover,graft failures continue to occur because of immunological rejection,despite the use of potent immunosuppressive agents.Mesenchymal stem cells(MSCs)have the potential to enhance islet transplantation by suppressing inflammatory damage and immune mediated rejection.In this review we discuss the impact of MSCs on islet transplantation and focus on the potential role of MSCs in protecting islet grafts from early graft failure and from autoimmune attack.展开更多
AIM To carry out randomized trial for evaluating effects of autologous bone marrow derived stem cell therapy(ABMSCT) through different routes.METHODS Bone marrow aspirate was taken from the iliac crest of patients. Bo...AIM To carry out randomized trial for evaluating effects of autologous bone marrow derived stem cell therapy(ABMSCT) through different routes.METHODS Bone marrow aspirate was taken from the iliac crest of patients. Bone marrow mononuclear cells were separatedand purified using centrifugation. These cells were then infused in a total of 21 patients comprising three groups of 7 patients each. Cells were infused into the superior pancreaticoduodenal artery(Group Ⅰ), splenic artery(Group Ⅱ) and through the peripheral intravenous route(Group Ⅲ). Another group of 7 patients acted as controls and a sham procedure was carried out on them(Group Ⅳ). The cells were labelled with the PET tracer F18-FDG to see their homing and in vivo distribution. Data for clinical outcome was expressed as mean ± SE. All other data was expressed as mean ± SD. Baseline and post treatment data was compared at the end of six months, using paired t-test. Cases and controls data were analyzed using independent t-test. A probability(P) value of < 0.05 was regarded as statistically significant. Measures of clinical outcome were taken as the change or improvement in the following parameters:(1) C-peptide assay;(2) HOMA-IR and HOMA-B;(3) reduction in Insulin dose; subjects who showed reduction of insulin requirement of more than 50% from baseline requirement were regarded as responders; and(4) reduction in HbA 1c. RESULTS All the patients, after being advised for healthy lifestyle changes, were evaluated at periodical intervals and at the end of 6 mo. The changes in body weight, body mass index, waist circumference and percentage of body fat in all groups were not significantly different at the end of this period. The results of intra-group comparison before and after ABMSCT at the end of six months duration was as follows:(1) the area under C-peptide response curve was increased at the end of 6 mo however the difference remained statistically non-significant(P values for fasting C-peptide were 0.973, 0.103, 0.263 and 0.287 respectively and the P values for stimulated C-peptide were 0.989, 0.395, 0.325 and 0.408 respectively for groups Ⅰ?to Ⅳ);(2) the Insulin sensitivity indices of HOMA IR and HOMA B also did not show any significant differences(P values for HOMA IR were 0.368, 0.223, 0.918 and 0.895 respectively and P values for HOMA B were 0.183, 0.664, 0.206 and 0.618 respectively for groups Ⅰto Ⅳ);(3) Group Ⅰshowed a significant reduction in Insulin dose requirement(P < 0.01). Group Ⅱ patients also achieved a significant reduction in Insulin dosages(P = 0.01). The Group Ⅰand Group Ⅱ patients together constituted the targeted group wherein the feeding arteries to pancreas were used for infusing stem cells. Group Ⅲ, which was the intravenous group, showed a non-significant reduction in Insulin dose requirement(P = 0.137). Group Ⅳ patients which comprised the control arm also showed a significant reduction in Insulin dosages at the end of six months(P < 0.05); and(4) there was a non-significant change in the Hb A1 c levels at the end of 6 mo across all groups(P = 0.355, P = 0.351, P = 0.999 and P = 0.408 respectively for groups Ⅰto Ⅳ). CONCLUSION Targeted route showed a significant reduction in Insulin requirement at the end of six months of study period whereas the intravenous group failed to show reduction.展开更多
AIM:To evaluate the safety and efficacy of human embryonic stem cells(h ESCs)for the management of type 2 diabetes mellitus(T2DM).METHODS:Patients with a previous history of diabetes and its associated complications w...AIM:To evaluate the safety and efficacy of human embryonic stem cells(h ESCs)for the management of type 2 diabetes mellitus(T2DM).METHODS:Patients with a previous history of diabetes and its associated complications were enrolled and injected with hE SC lines as per the defined protocol.The patients were assessed using Nutech functional score(NFS),a numeric scoring scale to evaluate the patients for 11 diagnostic parameters.Patients were evaluated at baseline and at the end of treatment period 1(T1).All the parameters were graded on the NFS scale from 1to 5.Highest possible grade(HPG)of 5 was considered as the grade of best improvement.RESULTS:Overall,94.8%of the patients showed improvement by at least one grade of NFS at the end of T1.For all the 11 parameters evaluated,54%of patients achieved HPG after treatment.The four essential parameters(improvement in glycated hemoglobin(HbA 1c)and insulin level,and fall in number of other oral hypoglycemic drugs with and without insulin)are presented in detail.For Hb A1c,72.6%of patients at the end of T1 met the World Health Organization cut off value,i.e.,6.5%of HbA 1c.For insulin level,65.9%of patients at the end of T1 were able to achieve HPG.After treatment,the improvement was seen in 16.3%of patients who required no more than two medications along with insulin.Similarly,21.5%of patients were improved as their dosage regimen for using oral drugs was reduced to 1-2 from 5.CONCLUSION:hE SC therapy is beneficial in patients with diabetes and helps in reducing their dependence on insulin and other medicines.展开更多
目的利用Meta分析评价间充质干细胞(MSC)移植治疗2型糖尿病(T2DM)的中远期效果和安全性,评估MSC治疗是否可作为T2DM的补充治疗方案。方法两位研究人员在PubMed、Web of Science、Cochrane Library、中国知网、万方数据和中国生物医学文...目的利用Meta分析评价间充质干细胞(MSC)移植治疗2型糖尿病(T2DM)的中远期效果和安全性,评估MSC治疗是否可作为T2DM的补充治疗方案。方法两位研究人员在PubMed、Web of Science、Cochrane Library、中国知网、万方数据和中国生物医学文献数据库检索文献,依据纳入、排除标准独立筛选文献和提取数据资料。利用Rev-Man 5.4软件进行Meta分析。结果共纳入11项关于MSC治疗T2DM的临床试验。与MSC治疗前基线比较,治疗后第3、6、12个月,糖化血红蛋白(HbA1c,MD:-1.12,95%CI:[-1.67,-0.57];MD:-1.34,95%CI:[-2.10,-0.57];MD:-1.06,95%CI:[-1.68,-0.45])和外源胰岛素用量(MD:-22.68,95%CI:[-29.89,-15.47];MD:-25.34,95%CI:[-38.41,-12.26];MD:-27.45,95%CI:[-36.65,-18.24])均显著降低(P<0.01),空腹血糖(FBG,MD:-1.10,95%CI:[-2.10,-0.10])和空腹C肽(MD:0.48,95%CI:[0.06,0.90])仅在治疗后第6个月出现改善(P<0.05);与对照组比较,MSC治疗后的第3、6、12个月外源胰岛素用量均显著降低(MD:-15.58,95%CI:[-18.26,-12.89];MD:-16.77,95%CI:[-30.09,-3.46];MD:-26.90,95%CI:[-29.59,-24.20],P<0.01),HbA1c在治疗后第6、12个月时明显降低(MD:-0.62,95%CI:[-1.15,-0.09];MD:-0.75,95%CI:[-1.40,-0.11],P<0.05),FBG在第6个月时明显降低(MD:-0.83,95%CI:[-1.57,-0.09],P<0.05)。自体/异体来源的MSC可能是导致HbA1c和FBG异质性的潜在影响因素之一。未见关于MSC治疗后严重不良反应报告,常见不良反应为一过性发热和低血糖事件。结论MSC治疗后第3~12个月内均表现出对T2DM患者血糖和外源胰岛素用量的控制,并具备较好的安全性。MSC可作为T2DM治疗的补充方案。展开更多
目的探究神经表皮生长因子样蛋白1(Nel-like type 1 molecule,NELL-1)对人脱落乳牙牙髓干细胞(stem cells from human exfoliated deciduous teeth,SHEDs)增殖及骨向分化的影响。方法对SHEDs进行分离、培养和细胞鉴定,将生长状态良好的...目的探究神经表皮生长因子样蛋白1(Nel-like type 1 molecule,NELL-1)对人脱落乳牙牙髓干细胞(stem cells from human exfoliated deciduous teeth,SHEDs)增殖及骨向分化的影响。方法对SHEDs进行分离、培养和细胞鉴定,将生长状态良好的第3代细胞用于后续实验。SHEDs分为4组,分别加入浓度为0(对照组)、50、100、200 ng/mL的NELL-1,利用CCK-8法和结晶紫染色法检测细胞活性;碱性磷酸酶活性检测细胞成骨能力改变;RT-qPCR检测成骨相关基因ALP、OCN、Runx-2表达水平;Western blot法检测成骨相关蛋白ALP、Runx-2、Col-Ⅰ表达情况。结果SHEDs具有干细胞特性,50 ng/mL的NELL-1可显著促进SHEDs增殖(P<0.01);碱性磷酸酶活性检测结果显示,加入NELL-1后,各组细胞成骨效果优于对照组,其中50 ng/mL NELL-1组成骨效果最佳(P<0.05);RT-qPCR和Western blot结果显示50 ng/mL NELL-1显著促进ALP、OCN、Runx-2成骨相关基因及ALP、Runx-2、Col-Ⅰ蛋白表达(P<0.05)。结论NELL-1对SHEDs增殖、成骨分化具有促进作用。展开更多
文摘Islet cell transplantation has therapeutic potential to treat type 1 diabetes,which is characterized by autoimmune destruction of insulin-producing pancreatic isletβcells.It represents a minimal invasive approach forβcell replacement,but long-term blood control is still largely unachievable.This phenomenon can be attributed to the lack of islet vasculature and hypoxic environment in the immediate post-transplantation period that contributes to the acute loss of islets by ischemia.Moreover,graft failures continue to occur because of immunological rejection,despite the use of potent immunosuppressive agents.Mesenchymal stem cells(MSCs)have the potential to enhance islet transplantation by suppressing inflammatory damage and immune mediated rejection.In this review we discuss the impact of MSCs on islet transplantation and focus on the potential role of MSCs in protecting islet grafts from early graft failure and from autoimmune attack.
文摘AIM To carry out randomized trial for evaluating effects of autologous bone marrow derived stem cell therapy(ABMSCT) through different routes.METHODS Bone marrow aspirate was taken from the iliac crest of patients. Bone marrow mononuclear cells were separatedand purified using centrifugation. These cells were then infused in a total of 21 patients comprising three groups of 7 patients each. Cells were infused into the superior pancreaticoduodenal artery(Group Ⅰ), splenic artery(Group Ⅱ) and through the peripheral intravenous route(Group Ⅲ). Another group of 7 patients acted as controls and a sham procedure was carried out on them(Group Ⅳ). The cells were labelled with the PET tracer F18-FDG to see their homing and in vivo distribution. Data for clinical outcome was expressed as mean ± SE. All other data was expressed as mean ± SD. Baseline and post treatment data was compared at the end of six months, using paired t-test. Cases and controls data were analyzed using independent t-test. A probability(P) value of < 0.05 was regarded as statistically significant. Measures of clinical outcome were taken as the change or improvement in the following parameters:(1) C-peptide assay;(2) HOMA-IR and HOMA-B;(3) reduction in Insulin dose; subjects who showed reduction of insulin requirement of more than 50% from baseline requirement were regarded as responders; and(4) reduction in HbA 1c. RESULTS All the patients, after being advised for healthy lifestyle changes, were evaluated at periodical intervals and at the end of 6 mo. The changes in body weight, body mass index, waist circumference and percentage of body fat in all groups were not significantly different at the end of this period. The results of intra-group comparison before and after ABMSCT at the end of six months duration was as follows:(1) the area under C-peptide response curve was increased at the end of 6 mo however the difference remained statistically non-significant(P values for fasting C-peptide were 0.973, 0.103, 0.263 and 0.287 respectively and the P values for stimulated C-peptide were 0.989, 0.395, 0.325 and 0.408 respectively for groups Ⅰ?to Ⅳ);(2) the Insulin sensitivity indices of HOMA IR and HOMA B also did not show any significant differences(P values for HOMA IR were 0.368, 0.223, 0.918 and 0.895 respectively and P values for HOMA B were 0.183, 0.664, 0.206 and 0.618 respectively for groups Ⅰto Ⅳ);(3) Group Ⅰshowed a significant reduction in Insulin dose requirement(P < 0.01). Group Ⅱ patients also achieved a significant reduction in Insulin dosages(P = 0.01). The Group Ⅰand Group Ⅱ patients together constituted the targeted group wherein the feeding arteries to pancreas were used for infusing stem cells. Group Ⅲ, which was the intravenous group, showed a non-significant reduction in Insulin dose requirement(P = 0.137). Group Ⅳ patients which comprised the control arm also showed a significant reduction in Insulin dosages at the end of six months(P < 0.05); and(4) there was a non-significant change in the Hb A1 c levels at the end of 6 mo across all groups(P = 0.355, P = 0.351, P = 0.999 and P = 0.408 respectively for groups Ⅰto Ⅳ). CONCLUSION Targeted route showed a significant reduction in Insulin requirement at the end of six months of study period whereas the intravenous group failed to show reduction.
文摘AIM:To evaluate the safety and efficacy of human embryonic stem cells(h ESCs)for the management of type 2 diabetes mellitus(T2DM).METHODS:Patients with a previous history of diabetes and its associated complications were enrolled and injected with hE SC lines as per the defined protocol.The patients were assessed using Nutech functional score(NFS),a numeric scoring scale to evaluate the patients for 11 diagnostic parameters.Patients were evaluated at baseline and at the end of treatment period 1(T1).All the parameters were graded on the NFS scale from 1to 5.Highest possible grade(HPG)of 5 was considered as the grade of best improvement.RESULTS:Overall,94.8%of the patients showed improvement by at least one grade of NFS at the end of T1.For all the 11 parameters evaluated,54%of patients achieved HPG after treatment.The four essential parameters(improvement in glycated hemoglobin(HbA 1c)and insulin level,and fall in number of other oral hypoglycemic drugs with and without insulin)are presented in detail.For Hb A1c,72.6%of patients at the end of T1 met the World Health Organization cut off value,i.e.,6.5%of HbA 1c.For insulin level,65.9%of patients at the end of T1 were able to achieve HPG.After treatment,the improvement was seen in 16.3%of patients who required no more than two medications along with insulin.Similarly,21.5%of patients were improved as their dosage regimen for using oral drugs was reduced to 1-2 from 5.CONCLUSION:hE SC therapy is beneficial in patients with diabetes and helps in reducing their dependence on insulin and other medicines.
文摘目的利用Meta分析评价间充质干细胞(MSC)移植治疗2型糖尿病(T2DM)的中远期效果和安全性,评估MSC治疗是否可作为T2DM的补充治疗方案。方法两位研究人员在PubMed、Web of Science、Cochrane Library、中国知网、万方数据和中国生物医学文献数据库检索文献,依据纳入、排除标准独立筛选文献和提取数据资料。利用Rev-Man 5.4软件进行Meta分析。结果共纳入11项关于MSC治疗T2DM的临床试验。与MSC治疗前基线比较,治疗后第3、6、12个月,糖化血红蛋白(HbA1c,MD:-1.12,95%CI:[-1.67,-0.57];MD:-1.34,95%CI:[-2.10,-0.57];MD:-1.06,95%CI:[-1.68,-0.45])和外源胰岛素用量(MD:-22.68,95%CI:[-29.89,-15.47];MD:-25.34,95%CI:[-38.41,-12.26];MD:-27.45,95%CI:[-36.65,-18.24])均显著降低(P<0.01),空腹血糖(FBG,MD:-1.10,95%CI:[-2.10,-0.10])和空腹C肽(MD:0.48,95%CI:[0.06,0.90])仅在治疗后第6个月出现改善(P<0.05);与对照组比较,MSC治疗后的第3、6、12个月外源胰岛素用量均显著降低(MD:-15.58,95%CI:[-18.26,-12.89];MD:-16.77,95%CI:[-30.09,-3.46];MD:-26.90,95%CI:[-29.59,-24.20],P<0.01),HbA1c在治疗后第6、12个月时明显降低(MD:-0.62,95%CI:[-1.15,-0.09];MD:-0.75,95%CI:[-1.40,-0.11],P<0.05),FBG在第6个月时明显降低(MD:-0.83,95%CI:[-1.57,-0.09],P<0.05)。自体/异体来源的MSC可能是导致HbA1c和FBG异质性的潜在影响因素之一。未见关于MSC治疗后严重不良反应报告,常见不良反应为一过性发热和低血糖事件。结论MSC治疗后第3~12个月内均表现出对T2DM患者血糖和外源胰岛素用量的控制,并具备较好的安全性。MSC可作为T2DM治疗的补充方案。
