Mesenchymal stem cell therapy for diabetes: An umbrella review

BACKGROUND: Diabetes mellitus (DM) is a chronic metabolic disorder characterized by impaired insulin production or function, leading to significant global health burdens and complications. Conventional treatments, including insulin therapy and oral hypoglycemic agents, often fail to restore normal glucose homeostasis and may cause side effects. Mesenchymal stem cell (MSC) therapy has emerged as a promising alternative, leveraging the regenerative and immunomodulatory properties of stem cells to address the underlying pathophysiology of diabetes. Given the increasing prevalence of diabetes and limitations of conventional therapies, evaluating novel regenerative interventions such as MSC therapy is both timely and clinically imperative. OBJECTIVE: This umbrella review synthesizes evidence from systematic reviews and meta-analyses to evaluate the efficacy and safety of MSC therapy for diabetes, focusing on clinical outcomes, mechanisms of action, and potential to overcome limitations of current treatments. METHODS: A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, and Web of Science up to July 30, 2025, following PRISMA guidelines. Inclusion criteria encompassed systematic reviews and meta-analyses assessing MSC therapy in type 1 (T1DM) or type 2 diabetes (T2DM) patients, with outcomes such as glycemic control, beta-cell function, and safety. Methodological quality was assessed using the AMSTAR-2 tool. Data were analyzed for study overlap, clinical outcomes, and safety profiles. RESULTS: The review included 17 systematic reviews and meta-analyses representing over 8000 patients. MSC therapy demonstrated significant improvements in glycemic control, particularly in T2DM, with reductions in HbA1c (up to 1.45 %) and insulin requirements (up to 2.05 U/kg/day). In T1DM, MSC therapy improved C-peptide levels and HbA1c but showed variable effects on insulin dependence. Wharton's jelly-derived MSCs and bone marrow-derived cells exhibited superior efficacy, while umbilical cord blood-derived MSCs were less effective. Adverse events were generally mild (e.g., fever, injection-site reactions), with severe events rare and linked to combination therapies. CONCLUSION: MSC therapy holds significant promise for diabetes management, especially for T2DM, with favorable safety profiles. However, heterogeneity in study designs and limited long-term data highlight the need for standardized protocols and large-scale randomized trials. Future research should focus on optimizing MSC sources, delivery methods, and long-term outcomes to facilitate clinical translation.