Stem cell transplantation for the treatment of patients with type�1 diabetes mellitus: A meta‑analysis

Abstract

The efficacy of stem cell (SC) transplantation in patients with type 1 diabetes mellitus (T1DM) has remained to be fully elucidated. In the present study, a systematic review and meta-analysis was performed to determine the clinical outcomes. Electronic databases, including PubMed, MEDLINE, WanFang and the Cochrane Library were screened for relevant studies published until January 13, 2018. The references of retrieved papers, systematic reviews and trial registries were manually screened for additional papers. Two authors were involved in screening the titles in order to select eligible studies, extract data and assess the risk of bias. Studies were pooled using a random-effects model as well as the Begg's funnel plot and subgroup analysis was performed using Stata 14.0 software. A total of 47 studies were retrieved for detailed evaluation, of which 22 met the inclusion criteria. No substantial publication bias was identified. The meta-analysis revealed that SC therapy increased C-peptide levels when compared with placebo treatment in randomized-controlled trials [RCT; standardized mean difference (SMD), 0.93; 95% confidence interval (CI) 0.23–1.63] and self-controlled trials (SMD, 0.66; 95% CI, −0.22 to 1.54). An analysis demonstrated that SC therapy was more efficient at reducing the glycated hemoglobin level compared with the control group in RCTs (SMD, 0.56; 95% CI; 0.06–1.06; and SMD, 1.63; 95% CI, 0.92–2.34, respectively). The graphs demonstrated that SC transplantation resulted in a reduction of insulin requirement. Furthermore, subgroup analyses revealed that patient age, medical history and the SC injection dose may be sources of the heterogeneity observed. The greatest benefit of SC transplantation was seen in patients aged ≥18 years or a medical history of <3 months. In addition, the SC injection dose of ≥107 IU/kg/day was more effective than <107 IU/kg/day when the cellular composition included mesenchymal SCs and hematopoietic SCs. In conclusion, SC therapy represents an efficient option for patients with T1DM. This systematic review was registered at the International prospective register of systematic reviews (no. 42018093930).

Efficacy and safety of stem cells transplantation in patients with type 1 diabetes mellitus—a systematic review and meta-analysis

“…As indicated by the pooled effect in our meta-analysis, MSCs + HSCs and HSCs groups showed significant effects to reduce daily insulin requirement and HbA1c levels, as well as to improve C-peptide levels at 1 year follow-up compared to the baseline. Whereas the MSCs group only showed significant effect to decrease HbA1c levels but no significant effect to reduce daily insulin requirement or to improve C-peptide levels, which was different from the meta-analysis conducted by Gan J et al [45]. As we know that, β cells function will decrease rapidly within years during the natural course of T1DM.…”

Allogenic Adipose Tissue-Derived Stromal/Stem Cells and Vitamin D Supplementation in Patients With Recent-Onset Type 1 Diabetes Mellitus: A 3-Month Follow-Up Pilot Study

“…The rationale for its use is to arrest β cells autoimmune destruction and generate functional cells. Mesenchymal stromal/stem cells seem attractive as they have been tested for other autoimmune diseases with promising results (16)(17)(18)(19)(20)(21)(22)(23)(24) and do not require immunosuppression, even when allogenic sources are used. In vivo and in vitro studies showed that MSCs are capable of suppressing immune response by inhibiting the maturation of dendritic cells, suppressing T cells function and inducing expansion of regulatory T cells (16)(17)(18)(19).…”

“…In vivo and in vitro studies showed that MSCs are capable of suppressing immune response by inhibiting the maturation of dendritic cells, suppressing T cells function and inducing expansion of regulatory T cells (16)(17)(18)(19). A recent meta-analysis of the clinical efficacy and safety of stem cell therapy for T1D indicated that the treatment seems relatively safe and effective, but most studies are small, use hematopoietic stem cells with immunosuppression and autologous origin (20). In that meta-analysis, patients with recent-onset T1D that received MSCs (from bone marrow or umbilical cord tissue) did not have significant reduction in HbA1c or improvement in C-peptide levels, but 20% of treated T1D patients achieved exogenous insulin independence at some point (20).…”

“…A recent meta-analysis of the clinical efficacy and safety of stem cell therapy for T1D indicated that the treatment seems relatively safe and effective, but most studies are small, use hematopoietic stem cells with immunosuppression and autologous origin (20). In that meta-analysis, patients with recent-onset T1D that received MSCs (from bone marrow or umbilical cord tissue) did not have significant reduction in HbA1c or improvement in C-peptide levels, but 20% of treated T1D patients achieved exogenous insulin independence at some point (20). Adipose tissue-derived stromal/stem cells (ASCs) have not been evaluated for this purpose.…”

A type 2 diabetes mellitus patient was successfully treated by autologous bone marrow-derived stem cell transplantation: A case report

“…Although the etiology of this disease is still under study, most scientists agree that T2DM is related to the resistance of insulin in muscle cells; briefly, insulin cannot trigger the glucose uptake process into cells 7,16 . For the past decade of stem cell therapy, most studies have used stem cell therapy in type 1 diabetes mellitus to regenerate beta cells in the pancreas [17][18][19] . In recent years, some studies have evaluated the use of stem cells to treat T2DM 14 .…”