Invited commentary

Abstract

As the quest for stem cell-based therapies to treat nonhealing wounds continues, less effort has examined local, cutaneous treatments that may improve autogenous stem cell function. This exciting translational work by Dr Velazquez and colleagues examines local wound therapy using topical estrogen to improve stem cell function in diabetic wounds. This study is particularly important in light of recent clinical trials in which autogenous stem cells have been only modestly successful in improving healing in diabetic patients. It is likely that local therapy that improves the function of these cells will be necessary to see a significant difference in healing in the population of diabetic patients. This group attempts to tackle a challenging problem related to the impairment of stem cells in diabetic populations and to augment cell function by topical estrogen. In short, this study used a standard cutaneous wound model in a murine model of diabetes and treated mice with either topical estrogen or placebo for 5 days. The wounds were then harvested, and endothelial progenitor cells (EPCs) were examined for viability and proliferation as well as recruitment to the tissue. Mesenchymal stem cells (MSCs), which are well studied for their role in tissue regeneration, were examined at later time points for their role in repair and collagen deposition. They found that the wounds treated with estrogen had higher vessel density and increased EPC recruitment and the MSC activity was enhanced, resulting in increased scar density and collagen deposition. Perhaps most important, wound healing was significantly improved in the mice receiving estrogen. This is very exciting as this work holds a high potential for easy translation to human patients. Additional work will need to be done to ensure that there is minimal toxicity related to estrogen therapy applied locally. It is well known that repair of injury is dependent on progression through distinct overlapping phases; however, the failure of these phases to occur in timely progressive fashion will promote disease. In addition to therapies designed to target the EPCs and MSCs, it is likely that optimal therapy for diabetic wounds will include the targeting of other immune cell populations known to play a critical role in the tissue repair process. It is unknown whether topical estrogen therapy alters other immune cell populations involved in tissue repair. Furthermore, the mechanisms regarding how estrogen therapy is improving EPC and MSC function will need to be elucidated. Despite its minor limitations, this exciting translational study by the Velazquez laboratory is critical for advancing our knowledge of diabetic wound repair. The opinions or views expressed in this commentary are those of the author and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. The effect of estrogen on diabetic wound healing is mediated through increasing the function of various bone marrow-derived progenitor cellsJournal of Vascular SurgeryVol. 68Issue 6PreviewEndothelial progenitor cells (EPCs) are the key cells of postnatal neovascularization, and mesenchymal stem cells (MSCs) possess pluripotent differentiation capacity and contribute to tissue regeneration and wound healing. Both EPCs and MSCs are critical to the wound repair process, which is hindered in diabetes mellitus. Diabetes has been shown to decrease the function of these progenitor cells, whereas estrogen has beneficial wound healing effects. However, the role of estrogen in modulating EPC and MSC biology in diabetes is unknown. Full-Text PDF Open Access