The Clinical Efficacy And Safety Of Stem Cell Therapy For Diabetes Mellitus

BackgroundDiabetes mellitus(DM)is a chronic metabolic disease with high morbidity and mortality.Recently,stem cell-based therapy for DM has shown considerable promise.Stem cells can differentiate into a variety of cells,including insulin-producing cells(IPCs).This paper further studies the feasibility of inducing umbilical cord-derived mesenchymal stem cells(MSCs)into IPCs in vitro,providing a basis for the clinical treatment of stem cells.Furthermore,we undertook a systematic review and meta-analysis of published clinical studies to evaluate the efficacy and safety of stem cell therapy for both type 1 DM(T1DM)and type 2 DM(T2DM).MethodsThis study was divided into two parts,the experimental part and the meta-analysis part.In the first part is in the experimental section,we isolated and cultured umbilical cord MSCs,and induced differentiation into IPCs under certain conditions.We useddithizone staining and real-time quantitative PCR to identify the induced cells.In the second part is meta section,computer retrieval Pub Med,Cochrane Central Register of Controlled Trials,EMBASE and Clinical Trials.gov database and manual retrieval,to "diabetes mellitus" and "hyperglycemia," "stem cells","progenitor cells","hematopoietic stem cells","Mesenchymal stem cells","bone marrow mononuclear cells" and "cell therapy" were keywords to collect all studies up to November 2018.Literature screening and quality evaluation were performed according to the proposed inclusion and exclusion criteria.We employed a fixed-effect model using 95%confidence intervals(CIs)when no statistically significant heterogeneity existed.Otherwise,a random-effects statistical model was used.ResultsIn the first part,umbilical cord-derived MSCs cultured in vitro with fibrous or spindle-shaped,high expression CD90,CD105 and CD73,no expression of HLA-DR,CD45,CD34,CD19,CD11 b,which could be differentiated into osteoblasts and adipocytes in vitro.After 28 days of IPCs induction in MSCs,islet like cell colonies were observed,dithizone staining showed a brown-red color,and m RNA expression of islet related genes such as Insulin was enhanced.In the second part,Meta-analysis shows twenty-one studies met our inclusion criteria: ten T1 DM studies including 226 patients and eleven T2 DM studies including386 patients.Stem cell therapy improved C-peptide levels(mean difference(MD),0.41;95% CI,0.06 to 0.76)and glycosylated hemoglobin(Hb A1c;MD,-3.46;95% CI,-6.01to-0.91)for T1 DM patients.For T2 DM patients,stem cell therapy improved C-peptide levels(MD,0.33;95% CI,0.07 to 0.59),Hb A1c(MD,-0.87;95% CI,-1.37 to-0.37)and insulin requirements(MD,-35.76;95% CI,-40.47 to-31.04).However,there wasno significant change in fasting plasma glucose levels(MD,-0.52;95% CI,-1.38 to0.34).Subgroup analyses showed significant Hb A1 c and C-peptide improvements in patients with T1 DM treated with bone marrow hematopoietic stem cells(BM-HSCs),while there was no significant change in the mesenchymal stem cell(MSC)group.In T2 DM,Hb A1 c and insulin requirements decreased significantly after MSC transplantation,and insulin requirements and C-peptide levels were significantly improved after bone marrow mononuclear cell(BM-MNC)treatment.ConclusionUmbilical cord-derived MSCs can be differentiated into IPCs in vitro and may become excellent candidates for diabetic stem cell replacement therapy.The results of this meta-analysis indicate that stem cells therapy is a relatively safe and effective method for selected individuals with DM.The data showed that BM-HSCs are superior to MSCs in the treatment of T1 DM.In T2 DM,MSC and BM-MNC transplantation showed favorable therapeutic effects.