Clinical Effectiveness and Safety of Stem Cell Therapy in Type 1 Diabetes Mellitus: A Systematic Review and Meta-analysis

Introduction: Type 1 diabetes mellitus (T1DM) represents an autoimmune disorder characterized by progressive deterioration of pancreatic β-cell through T-cell activity, which causes prolonged dependence on insulin. Meanwhile, stem cell treatment (SCT) is presently under investigation as a possible treatment approach. Therefore, this study investigated the safety profile and therapeutic effectiveness of SCT for T1DM. Methods: A broad database screening was carried out to identify studies published from January 1, 2012 to May 15, 2025 using PubMed, Scopus, and the Cochrane Library. Overall, 21 studies were incorporated in the systematic review, whereas 18 fulfilled the criteria required in the meta-analysis. Subgroup evaluation was organized according to stem cell category, design, and observation period. Results: The results showed that relative to baseline, SCT significantly reduced hemoglobin A1C (standardized mean difference [SMD] 1.52; P < 0.00001). The greatest decrease occurred after hematopoietic stem cell transplantation (HSCT) (SMD 2.90), which was also associated with a higher area under the curve C-peptide (SMD − 1.44; I 2 = 0%). The AD-mesenchymal stem cell + BM-HSC subgroup showed the largest increase in preprandial C-peptide (SMD − 2.98), whereas CB-SCs produced the strongest reduction in insulin requirement among randomized controlled trials (SMD 1.63). Most adverse reactions were nonsevere, although two HSCT-associated deaths suggest that safer protocols are required. Conclusions: These results suggest that SCT may enhance selected metabolic and β-cell function outcomes in individuals with T1DM. However, SCT should remain under investigation and be administered only within carefully monitored clinical trials.