Topical application of ex vivo expanded endothelial progenitor cells promotes vascularisation and wound healing in diabetic mice
Topical application of ex vivo expanded endothelial progenitor cells promotes vascularisation and wound healing in diabetic mice
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DOI：
10.1111/j.1742-481x.2012.01010.x
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发表时间：
2013-10-01
影响因子：
3.1
通讯作者：
Losordo, Douglas W.
中科院分区：
文献类型：
--
作者：
Asai, Jun;Takenaka, Hideya;Losordo, Douglas W.
导致皮肤溃疡的伤口愈合受损是糖尿病的严重并发症，并且可能由缺陷的血管生成引起。内皮祖细胞（EPCs）可以增加缺血组织中的新血管形成。进行实验以检验局部施用EPC可以促进糖尿病伤口愈合的假设。在糖尿病小鼠的背部上产生全层皮肤伤口。EPCs从骨髓单个核细胞（BMMNC）中获得，并在手术后立即局部应用于伤口。将媒介物和非选择性BMMNC用作对照。在治疗后第5、10和14天测量伤口大小，然后进行切除、组织学分析和定量血管分布。局部应用内皮祖细胞显着促进伤口愈合，愈合率和伤口血管。免疫组化显示移植的EPCs诱导血管内皮生长因子和碱性成纤维细胞生长因子表达增加。基于功能性脉管系统的体内染色，在新生脉管系统中观察到很少的EPC。体外扩增的EPCs通过增加局部细胞因子表达和增强伤口新生血管形成的机制促进糖尿病小鼠的伤口愈合。这种利用自体来源的EPCs的治疗能力的策略可能是糖尿病皮肤修复的新方法。
Impaired wound healing leading to skin ulceration is a serious complication of diabetes and may be caused by defective angiogenesis. Endothelial progenitor cells (EPCs) can augment neovascularisation in the ischaemic tissue. Experiments were performed to test the hypothesis that locally administered EPCs can promote wound healing in diabetes. Full-thickness skin wounds were created on the dorsum of diabetic mice. EPCs were obtained from bone marrow mononuclear cells (BMMNCs) and applied topically to the wound immediately after surgery. Vehicle and non-selective BMMNCs were used as controls. Wound size was measured on days 5, 10 and 14 after treatment, followed by resection, histological analysis and quantification of vascularity. Topical application of EPCs significantly promoted wound healing, as assessed by closure rate and wound vascularity. Immunostaining revealed that transplanted EPCs induced increased expression of vascular endothelial growth factor and basic fibroblast growth factor. Few EPCs were observed in the neovasculature based on in vivo staining of the functional vasculature. Ex vivo expanded EPCs promote wound healing in diabetic mice via mechanisms involving increased local cytokine expression and enhanced neovascularisation of the wound. This strategy exploiting the therapeutic capacity of autologously derived EPCs may be a novel approach to skin repair in diabetes.