Endothelial progenitor cells (EPCs) seeded on
biomaterials can effectively promote diabetic ischemic wound healing. However, the function of transplanted EPCs is negatively affected by a high-
glucose and ischemic microenvironment. Our experiments showed that
EPC autophagy was inhibited and mitochondrial membrane potential (
MMP) was increased in diabetic patients, while
adenosine treatment decreased the energy requirements and increased the autophagy levels of EPCs. In animal experiments, we transplanted a
biomaterial seeded with EPCs onto the surface of diabetic
wounds and found that
adenosine-stimulated EPCs effectively promoted wound healing. Increased microvascular genesis and survival of the transplanted cells were also observed in the
adenosine-stimulated groups. Interestingly, our study showed that
adenosine increased the autophagy of the transplanted EPCs seeded onto the
biomaterial and maintained
EPC survival at 48 and 96 hours. Moreover, we observed that
adenosine induced
EPC differentiation through increasing the level of autophagy. In conclusion, our study indicated that
adenosine-stimulated EPCs seeded onto a
biomaterial significantly improved wound healing in diabetic mice; mechanistically,
adenosine might maintain
EPC survival and differentiation by increasing high
glucose-inhibited
EPC autophagy and maintaining cellular energy metabolism.