Mesenchymal stem cell therapy for diabetes: clinical evidence, emerging strategies, and future perspectives.
Diabetes mellitus (DM) is a multifactorial metabolic disorder in which chronic hyperglycemia arises alongside adipose-tissue dysfunction, ectopic lipid accumulation, endothelial injury, and progressive multiorgan damage. These processes form an interconnected network, and because lowering glucose or blocking any single pathway leaves the other nodes active, the disease continues to advance even when glycemic targets are met. Therapies that act on several nodes at once are therefore conceptually attractive. Mesenchymal stem cell (MSC) therapy fits this requirement, engaging the immune, vascular, and metabolic arms of the disease at the same time through a shared paracrine program. Here, we analyze 107 registered interventional trials, drawn from 124 screened records, that evaluate MSC-based therapies across type 1 diabetes, type 2 diabetes, and a range of diabetic complications. Autologous bone marrow-derived MSCs (BMMSCs) and adipose-derived MSCs (AdMSCs) featured in the earliest trials, and registration has since shifted toward standardized allogeneic umbilical cord-derived MSCs (UCMSCs) and cell-free derivatives. The strongest and most consistent benefits appear in ischemic and wound-healing complications, particularly diabetic foot ulcers, whereas metabolic outcomes remain variable. Together, current early-phase evidence supports MSC therapy as a safe and potentially disease-modifying adjunct, although larger randomized trials with harmonized endpoints are needed to confirm efficacy.