Topical implantation of mesenchymal stem cells has beneficial effects on healing of experimental colitis in rats
Topical implantation of mesenchymal stem cells has beneficial effects on healing of experimental colitis in rats
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DOI：
10.1124/jpet.108.137083
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发表时间：
2008-08-01
影响因子：
3.5
通讯作者：
Kawano, Sunao
中科院分区：
文献类型：
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作者：
Hayashi, Yujiro;Tsuji, Shingo;Kawano, Sunao
骨髓间充质干细胞（MSC）是再生医学中有吸引力的细胞来源。我们研究了局部MSC植入对炎症性肠病实验模型的影响。假定的间充质干细胞，从骨髓抽吸的雄性大鼠培养皿粘附和体外扩增分离，其特征在于流式细胞术，逆转录-聚合酶链反应，酶联免疫吸附试验，和分化测定。用2，4，6-三硝基苯磺酸（TNBS）灌胃雄性大鼠结肠，诱发实验性结肠炎。将推定的MSC和新鲜的骨髓细胞注射到暴露于TNBS的区域周围的结肠粘膜下层中。用肉眼和免疫组织化学方法观察损伤的愈合过程。将CD 29和CD 90阳性，CD 31和CD 34阴性的多能MSC植入病变周围的结肠组织中;大多数移植的细胞对波形蛋白呈阳性。与注射载体的对照组相比，植入显著加速了受损粘膜的愈合。MSCs在体外及植入后表达血管内皮生长因子（VEGF）和转化生长因子（TGF）-β 1。总之，我们发现MSC成功地局部植入结肠中，并且它们与TNBS诱导的结肠炎的加速愈合相关。MSC的有益作用可能至少部分通过其分化成结肠间质细胞的能力以及其向损伤区域提供VEGF和TGF-β 1的能力来介导。
Mesenchymal stem cells (MSCs) are attractive cell sources in regenerative medicine. We examined the effects of topical MSCs implantation on an experimental model of inflammatory bowel disease. Putative MSCs, isolated from bone marrow aspirates of male rats by dish adherence and expanded in vitro, were characterized by flow cytometry, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and differentiation assays. Experimental colitis was induced by intraluminal instillation of 2,4,6-trinitrobonzene sulfonic acid (TNBS) in the colons of male rats. The putative MSCs and unselected fresh bone marrow cells were injected into the colonic submucosa surrounding the area exposed to TNBS. The healing process of the injury was examined macroscopically and immunohistologically. Multipotent MSCs positive for CD29 and CD90, and negative for CD31 and CD34, were implanted into colon tissue surrounding the lesion; a majority of the engrafted cells were positive for vimentin. The implantation significantly accelerated healing of the damaged mucosa compared with vehicle-injected controls. The MSCs expressed vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta 1 in vitro and after the implantation. In conclusion, we found that MSCs were successfully topically implanted in the colon and that they were associated with accelerated healing of TNBS-induced colitis. The beneficial effects of the MSCs might be mediated, at least in part, by their ability to differentiate into colonic interstitial cells and by their ability to provide VEGF and TGF-beta 1 to the injured area.