The effect of heme oxygenase-1 complexed with collagen on MSC performance in the treatment of diabetic ischemic ulcer.

Diabetic ischemic ulcer is an intractable diabetic complication. Bone marrow mesenchymal stem cells (BMSCs) have great potential in variety of tissue repair. In fact, poor cell viability and tolerance limit their ability for tissue repair. In addition, it is difficult for stem cells to home and locate to the lesion. In this study, we explore whether over-expression of heme oxygenase-1 (HO-1) in BMSCs complexed with collagen play an important role in treatment of diabetic ischemic ulcers. In vitro, over-expression of HO-1 promoted the proliferation and paracrine activity of BMSCs and the conditioned medium of BMSCs accelerated HUVECs migration and proliferation. These processes were closely related to Akt signaling pathway and were not dependent on Erk signaling pathway. In vivo, in order to make BMSCs directly act on the wound, we choose a solid collagen as a carrier, BMSCs were planted into it, ischemic wounds of diabetic mice were covered with the complex of BMSCs and collagen. The results indicate that the complex of HO-1-overexpressing BMSCs and collagen biomaterials can significantly promote angiogenesis and wound healing. These preclinical findings open new perspectives for the treatment of diabetic foot ulcers.