Allogeneic Human Bone Marrow‐Derived Mesenchymal Stem Cells Accelerate Diabetic Wound Healing via Inflammation Suppression and Angiogenesis Promotion: A Preclinical Study

Mesenchymal stem cells (MSCs) have been shown to enhance tissue regeneration and wound healing. This preclinical study investigated the therapeutic potential of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) for accelerating diabetic wound healing. Isolated hBM-MSCs were characterized for surface marker expression and differentiation potential. Their migration-promoting effects were evaluated in vitro. For the in vivo study, a dorsal skin defect model was created in streptozotocin (STZ)-induced diabetic rats. Rats received periwound subcutaneous injections of low- or high-dose hBM-MSCs on Days 4 and 7, or freezing fluid as a vehicle control. Wound healing progression was assessed clinically, and tissue biopsies were analyzed using immunohistochemistry to evaluate inflammatory cell infiltration, cellular proliferation, and angiogenesis. hBM-MSCs exhibited the expected surface marker profile and multilineage differentiation potential. In vitro, hBM-MSCs significantly enhanced the migration of human umbilical vein endothelial cells and human foreskin fibroblasts. In vivo, wounds treated with hBM-MSCs showed significantly accelerated healing compared to vehicle-treated controls (p < 0.05). Immunohistochemical analysis revealed reduced inflammatory cell infiltration and increased expression of Ki-67, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and prolyl 4-hydroxylase (P4H) in hBM-MSC-treated wounds. Allogeneic hBM-MSCs significantly promote diabetic wound healing by suppressing inflammation, enhancing cellular proliferation and differentiation, and stimulating angiogenesis. These findings highlight the therapeutic potential of allogeneic hBM-MSCs for treating diabetic wounds, particularly in patients unsuitable for autologous cell therapy.