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人间充质干细胞可能参与瘢痕疙瘩的发病机制。

Human mesenchymal stem cells may be involved in keloid pathogenesis.

作者信息

Akino Kozo, Akita Sadanori, Yakabe Aya, Mineda Takao, Hayashi Tomayoshi, Hirano Akiyoshi

机构信息

Division of Anatomy and Neurobiology, Nagasaki University, Nagasaki, Japan.

出版信息

Int J Dermatol. 2008 Nov;47(11):1112-7. doi: 10.1111/j.1365-4632.2008.03380.x.

DOI:10.1111/j.1365-4632.2008.03380.x
PMID:18986439
Abstract

BACKGROUND

The pathogenesis of keloid is poorly understood. Although vigorous investigations have attempted to elucidate the mechanisms or causative factors of keloid, there are little data on why keloids are very intractable and recur easily in each patient.

METHODS

In an attempt to analyze the possible interaction between human mesenchymal stem cells and keloid-derived fibroblasts, the dual-chamber cell-migration assay, cell proliferation, ultrastructural morphology, and Western blot analysis were used to investigate the production of the extracellular matrices of the coculture.

RESULTS

Cell proliferation was not significantly different between keloid-derived fibroblasts and normal dermal fibroblasts during a 4-day observation period. There was a significant cell migration of human mesenchymal stem cells when keloid-derived fibroblasts were placed in the bottom chamber, compared to when normal dermal fibroblasts were placed in the same way in 8-microm diameter pore membranes (190.6 +/- 51.45 and 32.0 +/- 6.20 cells/field, respectively, P < 0.01). With 3-microm diameter pores, the human mesenchymal stem cells migrated in the pores only when the keloid-derived fibroblasts were placed in the bottom chambers (6.4 +/- 3.84 cells/field). Monolayer coculture of human mesenchymal stem cells and keloid-derived fibroblasts demonstrated further functional differentiation, such as collagen secretion and abundant rough endoplasmic reticulum. Western blot analysis of the cells in the modified dual-chamber culture demonstrated most significantly abundant fibronectin expression when the human mesenchymal stem cells contained keloid fibroblasts.

CONCLUSION

The results of this study may indicate that human mesenchymal stem cells participate and recruit in keloid pathogenesis by differentiating themselves toward keloid recalcitrant formation and progression.

摘要

背景

瘢痕疙瘩的发病机制尚不清楚。尽管大量研究试图阐明瘢痕疙瘩的机制或致病因素,但关于瘢痕疙瘩为何在每个患者中都非常难以治疗且容易复发的数据却很少。

方法

为了分析人间充质干细胞与瘢痕疙瘩来源的成纤维细胞之间可能的相互作用,采用双室细胞迁移试验、细胞增殖、超微结构形态学和蛋白质印迹分析来研究共培养物细胞外基质的产生。

结果

在为期4天的观察期内,瘢痕疙瘩来源的成纤维细胞与正常真皮成纤维细胞之间的细胞增殖没有显著差异。当瘢痕疙瘩来源的成纤维细胞置于下室时,人间充质干细胞有显著的细胞迁移,而正常真皮成纤维细胞以同样方式置于8微米直径孔膜中时则不然(分别为190.6±51.45和32.0±6.20个细胞/视野,P<0.01)。对于3微米直径的孔,只有当瘢痕疙瘩来源的成纤维细胞置于下室时,人间充质干细胞才会在孔中迁移(6.4±3.84个细胞/视野)。人间充质干细胞与瘢痕疙瘩来源的成纤维细胞的单层共培养显示出进一步的功能分化,如胶原蛋白分泌和丰富的粗面内质网。改良双室培养中细胞的蛋白质印迹分析表明,当人间充质干细胞含有瘢痕疙瘩成纤维细胞时,纤连蛋白表达最为显著。

结论

本研究结果可能表明,人间充质干细胞通过向瘢痕疙瘩顽固性形成和进展方向分化而参与并促进瘢痕疙瘩的发病机制。

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