Mesenchymal Stem Cells Enhance Wound Healing Through Differentiation and Angiogenesis

• Published in: Stem cells (Dayton, Ohio) Ohio), 2007-10, Vol.25 (10), p.2648-2659
• Main Authors: Wu, Yaojiong, Chen, Liwen, Scott, Paul G., Tredget, Edward E.
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenic Proteins - biosynthesis; Angiogenic Proteins - genetics; Ang‐1; Animals; Cell Differentiation; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Diabetic mice; Female; Fibroblasts - transplantation; Genes, Reporter; Green Fluorescent Proteins - analysis; Green Fluorescent Proteins - genetics; Keratins - biosynthesis; Keratins - genetics; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - physiology; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Mice, Transgenic; Neovascularization, Physiologic - physiology; Random Allocation; Regeneration/repair; Skin - injuries; Skin - pathology; Transplantation, Homologous; Vascular endothelial growth factor; Wound Healing - physiology; Wounds and Injuries - pathology; Wounds and Injuries - therapy
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1634/stemcells.2007-0226

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. Disclosure of potential conflicts of interest is found at the end of this article.