Systemic Transplantation of Progenitor Cells Accelerates Wound Epithelialization and Neovascularization in the Hairless Mouse Ear Wound Model

Background. Impaired wound healing due to local injury, infection, or systemic diseases, such as diabetes, is a major clinical problem. Recent studies have shown that endothelial progenitor cells (EPC) isolated from peripheral blood, bone marrow, as well as the spleen accumulate in granulation tissue at the site of neovascularization, causing secretion of growth factors and cytokines and thus accelerating wound healing. Materials and Methods. In the present study, we transplanted systemic EPC and then measured epithelialization and neovascularization in the hairless mouse ear wound model. Results. Systemic EPC transplantation significantly accelerated epithelialization and neovascularization compared with control wounds receiving phosphate-buffered saline without calcium and magnesium (PBS). The EPC group had significantly higher vascular density than did the PBS-treated group as determined by immunohistochemistry for CD31 and CD90. Fluorescence microscopy revealed accumulation "homing'' of the transplanted EPC at the sites of neovascularization in the granulation tissue throughout healing. Furthermore, transplantation of EPC also increased the expression of the angiogenic cytokine stromal cell-derived factor 1 alpha (SDF1 alpha). Conclusions. This appears to be the first demonstration of EPC recruitment to the site of wound neovascularization throughout the healing process. These findings demonstrate that transplanting systemic EPC into "normal'' healing wounds promotes epithelialization and neovascularization and thus could be an useful method for accelerating wound healing. (C) 2011 Elsevier Inc. All rights reserved.