Wu Yaojiong, Chen Liwen, Scott Paul G, Tredget Edward E
161 HMRC, University of Alberta, 113 Street & 87 Avenue, Edmonton, Alberta T6G 2E1, Canada.
Stem Cells. 2007 Oct;25(10):2648-59. doi: 10.1634/stemcells.2007-0226. Epub 2007 Jul 5.
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.
尽管慢性伤口很常见，但针对这些致残性病症的治疗仍然有限且大多无效。在本研究中，我们检测了骨髓间充质干细胞（BM-MSCs）在伤口愈合中的益处。使用切除伤口夹板模型，我们发现，与同种异体新生真皮成纤维细胞或赋形剂对照培养基相比，在伤口周围注射并应用于伤口床的绿色荧光蛋白（GFP）(+) 同种异体BM-MSCs可显著促进正常和糖尿病小鼠的伤口愈合。对伤口来源的表达GFP的BM-MSCs进行荧光激活细胞分选分析表明，在注射的总BM-MSCs中，7天时植入率为27%，14天时为7.6%，28天时为2.5%。经BM-MSC治疗的伤口显示伤口闭合明显加速，再上皮化、细胞增多和血管生成增加。值得注意的是，BM-MSCs而非伤口中的CD34(+) 骨髓细胞表达角质形成细胞特异性蛋白角蛋白并形成腺状结构，提示BM-MSCs对皮肤再生有直接作用。此外，BM-MSC条件培养基可促进内皮细胞管形成。实时聚合酶链反应和蛋白质印迹分析显示，BM-MSCs中血管内皮生长因子和血管生成素-1水平较高，且经BM-MSC治疗的伤口中这些蛋白的含量显著更高。因此，我们的数据表明，BM-MSCs通过分化和释放促血管生成因子促进伤口愈合。潜在利益冲突披露见本文末尾。
