Human mesenchymal stem cells successfully improve skin-substitute wound healing
Human mesenchymal stem cells successfully improve skin-substitute wound healing
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DOI：
10.1111/j.1365-2133.2005.06554.x
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发表时间：
2005-07-01
影响因子：
10.3
通讯作者：
Akino, K
中科院分区：
文献类型：
--
作者：
Nakagawa, H;Akita, S;Akino, K
大面积或恶化的皮肤缺损有时会危及生命。越来越多的证据表明成体干细胞对组织再生有用。人骨髓间充质干细胞（human mesenchymal stem cells，hMSCs）具有自我更新能力，能分化为多种细胞和tissue. ObjectiveTo investigate effects of hMSCs in cutaneous wound health.Methods伤口愈合在hMSCs填充的猪皮肤替代物中进行了研究，使用裸大鼠模型以最大限度地减少免疫反应。切除1.5 × 1.5 cm大小的全层皮肤和软组织缺损，包括肉脂膜，并用hMSC和碱性成纤维细胞生长因子（bFGF）浸泡的皮肤替代物覆盖，并在3，结果hMSC治疗组创面面积明显小于对照组，差异有统计学意义（P < 0. 05 bFGF（1、10、100 μ g）均能促进愈合（P < 0.01）。再上皮化标志物整合素α 3和皮肤源性抗白细胞蛋白酶的存在与bFGF的剂量依赖性方式显着增加，而间充质细胞表面标志物CD 29和CD 44的下调，以时间依赖性的方式。人泛细胞角蛋白，不与大鼠抗原交叉反应，通过蛋白质印迹法在38 kDa和42 kDa的hMSC处理的组织在第7天观察到。10 μ g bFGF可显著提高细胞的表达水平（P < 0.01）。hMSC处理组中仅观察到人泛细胞角蛋白的免疫组化表达。结论hMSC与bFGF共同作用于皮肤缺损模型，促进皮肤创面愈合，因为hMSC转分化为上皮细胞。
Background Large or deteriorated skin defects are sometimes life threatening. There is increasing evidence that adult stem cells are useful for tissue regeneration. Human mesenchymal stem cells (hMSCs) are self-renewing and are potent in differentiating into multiple cells and tissues.Objectives To investigate the effects of hMSCs in cutaneous wound healing.Methods Wound healing was studied in an hMSC-populated porcine skin substitute, using a nude rat model to minimize immune reactions. Full-thickness skin and soft tissue defects of 1.5 x 1.5 cm in size, including the panniculus carnosus, were excised and covered with hMSCs and basic fibroblast growth factor (bFGF)-soaked skin substitutes and an evaluation was made of wound size, histology and protein expression at 3, 7 and 42 days after injury.Results The wound size was significantly smaller in the hMSC-treated groups (P < 0.01) and any dose of bFGF (1, 10, 100 mu g) enhanced the healing (P < 0.01). The re-epithelialization markers integrin alpha 3 and skin-derived antileucoproteinase were remarkably increased with the presence of bFGF in a dose-dependent manner, while the mesenchymal cell surface markers CD29 and CD44 were downregulated in a time-dependent manner. Human pancytokeratin, which does not cross-react with rat antigens, was observed by Western blotting at 38 kDa and 42 kDa from the hMSC-treated tissues on day 7. The expression levels were elevated by 10 mu g bFGF (P < 0.01). The immunohistochemical expression of human pancytokeratin was only observed in the hMSC-treated groups.Conclusions These data suggest that hMSCs together with bFGF in a skin defect model accelerate cutaneous wound healing as the hMSCs transdifferentiate into the epithelium.