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TRANSLATIONAL AND CLINICAL RESEARCH |
Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
Key Words. Angiogenesis • Regeneration/repair • Diabetic mice • Vascular endothelial growth factor • Ang-1
Correspondence: Yaojiong Wu, M.D., Ph.D., 161 HMRC, University of Alberta, 113 Street & 87 Avenue, Edmonton, Alberta T6G 2E1, Canada. Telephone: 780-492-8603; Fax: 780-492-6361; e-mail: yaojiong{at}ualberta.ca or e-mail: yjwu2005{at}yahoo.com; Edward E. Tredget, M.D., M.Sc., FRCSC, Department of Surgery, 2D3.81, 8440 112 Street, University of Alberta, Edmonton, Alberta T6G 2B7, Canada. Telephone: 780-407-6979; Fax: 780-407-7394; e-mail: etredget{at}gpu.srv.ualberta.ca
Received on May 28, 2007;
accepted for publication on June 19, 2007.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS July 5, 2007.
Although chronic wounds are common, treatment for these disabling conditions remains limited and largely ineffective. In this study, we examined the benefit of bone marrow-derived mesenchymal stem cells (BM-MSCs) in wound healing. Using an excisional wound splinting model, we showed that injection around the wound and application to the wound bed of green fluorescence protein (GFP)+ allogeneic BM-MSCs significantly enhanced wound healing in normal and diabetic mice compared with that of allogeneic neonatal dermal fibroblasts or vehicle control medium. Fluorescence-activated cell sorting analysis of cells derived from the wound for GFP-expressing BM-MSCs indicated engraftments of 27% at 7 days, 7.6% at 14 days, and 2.5% at 28 days of total BM-MSCs administered. BM-MSC-treated wounds exhibited significantly accelerated wound closure, with increased re-epithelialization, cellularity, and angiogenesis. Notably, BM-MSCs, but not CD34+ bone marrow cells in the wound, expressed the keratinocyte-specific protein keratin and formed glandular structures, suggesting a direct contribution of BM-MSCs to cutaneous regeneration. Moreover, BM-MSC-conditioned medium promoted endothelial cell tube formation. Real-time polymerase chain reaction and Western blot analysis revealed high levels of vascular endothelial growth factor and angiopoietin-1 in BM-MSCs and significantly greater amounts of the proteins in BM-MSC-treated wounds. Thus, our data suggest that BM-MSCs promote wound healing through differentiation and release of proangiogenic factors.
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