Nakagawa H, Akita S, Fukui M, Fujii T, Akino K
Division of Plastic and Reconstructive Surgery, Department of Developmental and Reconstructive Medicine, Nagasaki University, Graduate School of Medical and Dental Sciences, 1-7-1 Sakamoto, Nagasaki 8528501, Japan.
Br J Dermatol. 2005 Jul;153(1):29-36. doi: 10.1111/j.1365-2133.2005.06554.x.
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.
To investigate the effects of hMSCs in cutaneous wound healing.
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.
The wound size was significantly smaller in the hMSC-treated groups (P < 0.01) and any dose of bFGF (1, 10, 100 microg) enhanced the healing (P < 0.01). The re-epithelialization markers integrin alpha3 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 microg bFGF (P < 0.01). The immunohistochemical expression of human pancytokeratin was only observed in the hMSC-treated groups.
These data suggest that hMSCs together with bFGF in a skin defect model accelerate cutaneous wound healing as the hMSCs transdifferentiate into the epithelium.
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（hMSCs）具有自我更新能力，并且能够有效地分化为多种细胞和组织。
研究hMSCs在皮肤伤口愈合中的作用。
在一个植入hMSCs的猪皮肤替代物中研究伤口愈合情况，使用裸鼠模型以尽量减少免疫反应。切除大小为1.5×1.5 cm的全层皮肤和软组织缺损，包括腹直肌，并用浸泡了hMSCs和碱性成纤维细胞生长因子（bFGF）的皮肤替代物覆盖，在损伤后3天、7天和42天对伤口大小、组织学和蛋白表达进行评估。
hMSC治疗组的伤口大小明显更小（P<0.01），任何剂量的bFGF（1、10、100μg）均可促进愈合（P<0.01）。随着bFGF的存在，再上皮化标志物整合素α3和皮肤源性抗白细胞蛋白酶以剂量依赖性方式显著增加，而间充质细胞表面标志物CD29和CD44以时间依赖性方式下调。在第7天，通过蛋白质印迹法在hMSC处理的组织中观察到与大鼠抗原无交叉反应的人全细胞角蛋白，分子量分别为38 kDa和42 kDa。10μg bFGF可提高其表达水平（P<0.01）。仅在hMSC治疗组中观察到了人全细胞角蛋白的免疫组化表达。
这些数据表明，在皮肤缺损模型中，hMSCs与bFGF一起可加速皮肤伤口愈合，因为hMSCs可转分化为上皮细胞。
