Estrogen Facilitates the Healing of Diabetic Wounds via Ameliorating the Function of Bone Marrow Mesenchymal Stem Cells

Abstract

We inted to elucidate the impacts of estrogen on the bone marrow-originated endothelial progenitor cells (BM-EPC) and mesenchymal stem cells (BM-MSC) as well as on diabetic wound healing. The skin injury models were established using the diabetic mice (db+/db+) and non-diabetic vector mice and then treated with estrogen-based or placebo-based cream. On the 5th day following injury, BM cells were collected for quantification of EPCs and MSCs and colony-forming units along with analysis of wound healing rate and densities of blood vessels and scars following whole-body perfusion. EPCs were identified through staining of VEGFR1 and CD34 by immunohistochemistrical analyses. In contrast to placebo, treatment with estrogen significantly intensified the colony formation of EPC and MSC, and further promoted the viability and proliferation potential of cells. Meanwhile, estrogen-treated mice exhibited increased recruitment of EPC to the diabetic wounds along with increased vascular density. Additionally, on day 6 after injury, estrogen significantly accelerated wound healing, which was mediated by the enhanced collagen deposition through boosting MSC activation and differentiation, resulting in elevated scar density. In conclusion, estrogen prompts wound healing of diabetic mice via ameliorating the function of BM-derived EPC and MSC, so as to accelerate the neovascularization at the sites of wounds in diabetic mice.