A Dressing in Combination with Adenosine-Preconditioned Mesenchymal Stem Cells Accelerate the Healing of Diabetic Ulcers

Refractory ulcers are a major challenge in the treatment of diabetic foot disease. Deterioration of the wound environment around diabetic ulcers results in a low survival rate of transplanted mesenchymal stem cells (MSCs). Previous studies have shown that adenosine (ADO) plays a crucial role in promoting angiogenesis during the process of ischemic myocardial protection and tissue repair. However, it remains unclear whether ADO can enhance the therapeutic effects of transplantation by protecting transplanted human MSCs (hMSCs) under high-glucose conditions. In vitro experiments herein showed that under high-glucose conditions, ADO promoted the secretion of vascular endothelial growth factor, basic fibroblast growth factor and interleukin-8 from MSCs via different receptors. Under high-glucose conditions, conditioned media (derived from ADO-stimulated hMSCs) significantly promoted human umbilical vein endothelial cell proliferation and migration. In vivo experiments showed that biological material containing ADO-preconditioned MSCs significantly accelerated ulcer healing in diabetic mice. Furthermore, histological observation showed that diabetic mice treated with hMSCs from the ADO-preconditioned group exhibited markedly increased vascular density compared with that of the untreated group. The results demonstrated that a dressing containing ADO-preconditioned MSCs accelerated the healing of diabetic ulcers in mice. The mechanism may involve the enhancement of ulcer peripheral angiogenesis by promoting the paracrine effects of hMSCs.