Locally Administered Adipose-Derived Stem Cells Accelerate Wound Healing Through Differentiation and Vasculogenesis
Locally Administered Adipose-Derived Stem Cells Accelerate Wound Healing Through Differentiation and Vasculogenesis
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DOI：
10.3727/096368910x520065
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发表时间：
2011-01-01
影响因子：
3.3
通讯作者：
Zhang, Jiewu
中科院分区：
文献类型：
--
作者：
Nie, Chunlei;Yang, Daping;Zhang, Jiewu
尽管伤口闭合技术和设备取得了进步，但仍迫切需要新的方法来加强愈合过程，以实现最佳结果。近年来，干细胞治疗已成为一种促进伤口愈合的新方法。脂肪来源的干细胞(ASCs)是一种多潜能干细胞，能够分化为多种细胞系并分泌血管生成生长因子，在伤口愈合方面具有广阔的应用前景。本研究的目的是评估ASCs对创面愈合的益处，并探讨其可能的机制。经流式细胞仪鉴定，成功分离培养出ASCs。采用大鼠创面切除愈合模型，观察局部应用ASCs的效果。大体和组织学结果显示，ASCs显著促进正常和糖尿病大鼠创面闭合，包括增加上皮化和肉芽组织沉积。此外，我们将GFP标记的ASCs应用于创面，以确定ASCs是否可以在特定的微环境中沿着组织再生的多个谱系分化。免疫荧光分析表明，表达GFP的ASCs分别与泛细胞角蛋白和CD31共染色，表明其自发地向上皮样和内皮样分化。这些数据表明，ASCs不仅有助于皮肤再生，而且还参与新血管的形成。此外，ASCs在体外和体内都能分泌血管生成细胞因子，包括血管内皮生长因子、肝细胞生长因子和成纤维细胞生长因子2，它们可以增加损伤组织中的新生血管和促进伤口愈合。综上所述，ASC疗法可以通过分化和血管生成促进创面愈合，可能是一种新的皮肤创面治疗方法。
Despite advances in wound closure techniques and devices, there is still a critical need for new methods of enhancing the healing process to achieve optimal outcomes. Recently, stem cell therapy has emerged as a new approach to accelerate wound healing. Adipose-derived stem cells (ASCs) hold great promise for wound healing, because they are multipotential stem cells capable of differentiation into various cell lineages and secretion of angiogenic growth factors. The aim of this study was to evaluate the benefit of ASCs on wound healing and then investigate the probable mechanisms. ASCs characterized by flow cytometry were successfully isolated and cultured. An excisional wound healing model in rat was used to determine the effects of locally administered ASCs. The gross and histological results showed that ASCs significantly accelerated wound closure in normal and diabetic rat, including increased epithelialization and granulation tissue deposition. Furthermore, we applied GFP-labeled ASCs on wounds to determine whether ASCs could differentiate along multiple lineages of tissue regeneration in the specific microenvironment. Immunofluorescent analysis indicated that GFP-expressing ASCs were costained with pan-cytokeratin and CD31, respectively, indicating spontaneous site-specific differentiation into epithelial and endothelial lineages. These data suggest that ASCs not only contribute to cutaneous regeneration, but also participate in new vessels formation. Moreover, ASCs were found to secret angiogenic cytokines in vitro and in vivo, including VEGF, HGF, and FGF2, which increase neovascularization and enhance wound healing in injured tissues. In conclusion, our results demonstrate that ASC therapy could accelerate wound healing through differentiation and vasculogenesis and might represent a novel therapeutic approach in cutaneous wounds.