Abstract
Background: Diabetic foot disease is a major health problem. Diminished peripheral blood flow and decreased local neovascularization are critical factors in these patients. The correction of impaired local angiogenesis may be a key component in developing therapeutic protocols for treating chronic wounds of the lower extremity and diabetic foot ulcers.
The Problem: Endothelial progenitor cells (EPCs) are the key cellular effectors of postnatal neovascularization and play a central role in wound healing, but their circulating and wound level numbers are decreased in diabetes, implicating an abnormality in EPC mobilization and homing mechanisms.
Basic/Clinical Science Advances: Hyperoxia, induced by hyperbaric oxygen therapy protocol, can significantly enhance the mobilization of EPC from the bone marrow into peripheral blood. However, increased circulating EPCs failed to reach to wound tissues. This is partly as a result of down-regulated stromal cell derived factor-1 alpha in local wound lesions with diabetes. Administration of exogenous stromal cell derived factor-1 alpha into wounds reversed the EPC homing impairment and, with hyperoxia, synergistically enhanced EPC mobilization, homing, neovascularization, and wound healing.
Clinical Care Relevance: Our novel approach serves a potential solution to correct the impairment and to increase homing of EPC to wound tissues. It provides a scientific basis for the establishment of combination treatment protocols that include systemic hyperoxia and wound chemokine replacement.
Conclusion: Angiogenesis plays a critical role in wound repair. Our findings bring new insights into the problem of delayed wound healing and offer novel therapeutic options in the treatment of wounds, in particular, chronic and nonhealing wounds, and would thus have tremendous benefit to both individual patients and society.
