Mesenchymal Stem Cells Enhance Wound Healing Through Differentiation and Angiogenesis

¹ Department of Surgery, University of Alberta, Edmonton, AB, Canada

^* To whom correspondence should be addressed. E-mail: yaojiong{at}ualberta.ca.

	Abstract

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 GFP⁺ allogeneic BM-MSCs significantly enhanced wound healing in normal and diabetic mice compared to that of allogeneic neonatal dermal fibroblasts or vehicle control medium. FACS 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 PCR and Western blot analysis revealed high levels of VEGF 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 pro-angiogenic factors.