Role of bone marrow derived precursor cells in wound healing

Abstract

Abstract Introduction: Neovascularization, necessary for wound healing, involves angiogenesis and vasculogenesis. Bone marrow-derived endothelial progenitor cells (EPCs) are key to vasculogenesis. We hypothesized ischemic wounds have a deficit of EPCs. Methods: EPCs were quantified using LacZ-Tie-2 transgenic mice, where beta-galactosidase (beta-gal) is expressed by the Tie-2 promoter. Wild type mice were transplanted with bone marrow from LacZ-Tie-2 mice. 4 wks later, chimeric mice underwent unilateral femoral artery ligation and bilateral 3mm punch-biopsy of hindlimbs. Ischemia was monitored with laser Doppler. Wound closure was assessed for 14 d with digital imaging. 5 mice/group were sacrificed on postoperative day 3 to harvest: wound, skeletal muscle, un-wounded adjacent skin, and remote skin. EPC counts were quantified by beta-gal staining in serial cross sections. Results: We observed significantly decreased EPCs in ischemic wounds, without a difference in the overall cellularity. Significantly higher numbers of EPCs were observed in the ischemic muscle. As expected, ischemic wounds showed significantly decreased healing rates. Non-ischemic healing wounds had significantly increased EPCs. EPC numbers showed a three-fold increase in ischemic hindlimb skeletal muscle with or without overlying wounds. Conclusions: Ischemic wounds suffer from significantly reduced EPC numbers at day 3 post-wounding and these wounds show delayed healing. Conversely, increased numbers of EPCs are observed in non-ischemic healing wounds. To our knowledge, this is the first report demonstrating an early EPC deficit in ischemic wounds thus targeting vasculogenesis as a potential key component of delay wound healing in ischemia.