BMSCs Promote Diabetic Wound Healing via PGF-Mediated Regulation of Focal Adhesion Signaling

Diabetic chronic wounds, characterized by persistent inflammation and impaired blood vessel formation, pose a significant clinical challenge. While bone marrow mesenchymal stem cells are known for their regenerative potential, the specific mechanisms by which they influence cellular adhesion and signaling remain largely undefined. This study investigated whether bone marrow mesenchymal stem cells promote diabetic wound healing by enhancing placental growth factor-mediated activation of the focal adhesion signaling pathway. Through transcriptomic sequencing, bone marrow mesenchymal stem cells were found to possess significantly higher baseline levels of placental growth factor compared to adipose-derived or umbilical cord-derived stem cells. In cellular experiments, co-culturing these stem cells with human umbilical vein endothelial cells triggered an upregulation of placental growth factor and a subsequent activation of focal adhesion signaling, which improved the angiogenic capacity of the endothelial cells. In a diabetic rat model of ischemic wounds, the transplantation of bone marrow mesenchymal stem cells significantly accelerated the healing process. However, these therapeutic benefits were largely abolished when placental growth factor was silenced or when the focal adhesion pathway was chemically inhibited. These findings reveal a novel mechanism where bone marrow mesenchymal stem cells facilitate the repair of diabetic ischemic wounds by modulating endothelial placental growth factor expression to drive focal adhesion signaling. This study identifies the placental growth factor-focal adhesion axis as a critical target for future regenerative therapies in treating chronic diabetic complications.