Allogeneic Human Bone Marrow-Derived Mesenchymal Stem Cells Accelerate Diabetic Wound Healing via Inflammation...

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.