Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages

Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages
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DOI:
10.1007/s00441-006-0270-9
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发表时间:
2006-12-01
影响因子:
3.6
通讯作者:
Sun, Tongzhu
Sun, Tongzhu
中科院分区:
生物学3区
文献类型:
--
作者:
Li, Haihong;Fu, Xiaobing;Sun, Tongzhu

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成熟的骨髓源性间充质干细胞 (MSC) 已被证实具有分化为具有中胚层、外胚层和内胚层特征的细胞的能力,并且可以离开其生态位,以适应外来组织并植入其中。为了研究成体间充质干细胞是否有助于损伤后皮肤附属器的修复,将BrdU标记的间充质干细胞与热休克的汇合汗腺细胞(SGC)在体外共培养,然后静脉注射到大鼠全层皮肤伤口中。当成体 MSC 与热休克的 SGC 共培养时,一部分成体 MSC 分化为 SGC,分化百分比因表皮生长因子和受损的微环境而增强,但因 PD98059 而减弱。 ERK(细胞外信号调节激酶)通路,尤其是pERK,参与人MSCs向人SGC的表型转化。在全层伤口的毛囊、皮脂腺、血管和真皮中发现标记的间充质干细胞,并且毛囊和皮脂腺中的整合细胞也呈全细胞角蛋白阳性。伤口愈合后,一些标记的间充质干细胞返回骨髓,而另一些则保留在真皮中。我们得出的结论是,成体间充质干细胞有能力停靠在特定部位,促进皮肤附属器的伤口愈合,并归巢到骨髓,并且骨髓来源细胞的植入是一个功能事件。
Adult bone-marrow-derived mesenchymal stem cells (MSCs) are well-established as having the capacity to differentiate into cells with mesodermal, ectodermal, and endodermal characteristics and can leave their niche to home toward and engraft within foreign tissues. To investigate whether adult MSCs contribute to the repair of skin appendages after injury, BrdU-labeled MSCs were cocultured with heat-shocked confluent sweat gland cells (SGCs) in vitro and later intravenously injected into full-thickness skin wounds in rats. When adult MSCs were cocultured with heat-shocked SGCs, a subset of adult MSCs differentiated into SGCs, the percentage of differentiation being enhanced by epidermal growth factor and the injured microenviroment, but weakened by PD98059. The ERK (extracellular signal-regulated kinase) pathway, especially pERK, was involved in the phenotype conversion of human MSCs into human SGC. Labeled MSCs were noted in hair follicles, sebaceous glands, blood vessels, and dermis in full-thickness wounds, and the incorporated cells in hair follicles and sebaceous glands were also positive for pancytokeratin. After wound healing, some labeled MSCs returned to the bone marrow, whereas other were retained in the dermis. We conclude that adult MSCs have the capacity to dock at specific sites, to contribute to wound healing of skin appendages, and to home toward marrow, and that engraftment of bone-marrow-derived cells is a functional event.