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人皮肤来源成纤维细胞的多向分化潜能

Multilineage differentiation potential of human dermal skin-derived fibroblasts.

作者信息

Lorenz Katrin, Sicker Marit, Schmelzer Eva, Rupf Thomas, Salvetter Juergen, Schulz-Siegmund Michaela, Bader Augustinus

机构信息

Department of Cell Techniques and Applied Stem Cell Biology, Biotechnological-Biomedical Center, University of Leipzig, Leipzig, Germany.

出版信息

Exp Dermatol. 2008 Nov;17(11):925-32. doi: 10.1111/j.1600-0625.2008.00724.x. Epub 2008 Jun 14.

Abstract

Dermal skin-derived fibroblasts from rodent and human have been found to exhibit mesenchymal surface antigen immunophenotype and differentiation potential along the three main mesenchymal-derived tissues: bone, cartilage and fat. Human dermal skin-derived mesenchymal stem cells constitute a promising cell source in clinical applications. Therefore, we isolated fibroblastic mesenchymal stem-cell-like cells from human dermis derived from juvenile foreskins, which share a mesenchymal stem cell phenotype and multi-lineage differentiation potential. We could show similar expression patterns for CD14(-), CD29(+), CD31(-), CD34(-), CD44(+), CD45(-), CD71(+), CD73/SH3-SH4(+), CD90/Thy-1(+), CD105/SH2(+), CD133(-) and CD166/ALCAM(+) in well-established adipose tissue derived-stem cells and fibroblastic mesenchymal stem-cell-like cells by flow cytometry. Immunostainings showed that fibroblastic mesenchymal stem-cell-like cells expressed vimentin, fibronectin and collagen; they were less positive for alpha-smooth muscle actin and nestin, while they were negative for epithelial cytokeratins. When cultured under appropriate inducible conditions, both cell types could differentiate along the adipogenic and osteogenic lineages. Additionally, fibroblastic mesenchymal stem-cell-like cells demonstrated a high proliferation potential. These findings are of particular importance, because skin or adipose tissues are easily accessible for autologous cell transplantations in regenerative medicine. In summary, these data indicate that dermal fibroblasts with multilineage differentiation potential are present in human dermis and they might play a key role in cutaneous wound healing.

摘要

已发现源自啮齿动物和人类皮肤的真皮成纤维细胞表现出间充质表面抗原免疫表型,并具有沿三种主要间充质来源组织(骨、软骨和脂肪)分化的潜能。人皮肤来源的间充质干细胞是临床应用中一种很有前景的细胞来源。因此,我们从青少年包皮来源的人真皮中分离出成纤维细胞样间充质干细胞,它们具有间充质干细胞表型和多系分化潜能。通过流式细胞术,我们可以在成熟的脂肪组织来源干细胞和成纤维细胞样间充质干细胞中显示出相似的CD14(-)、CD29(+)、CD31(-)、CD34(-)、CD44(+)、CD45(-)、CD71(+)、CD73/SH3 - SH4(+)、CD90/Thy - 1(+)、CD105/SH2(+)、CD133(-)和CD166/ALCAM(+)表达模式。免疫染色显示,成纤维细胞样间充质干细胞表达波形蛋白、纤连蛋白和胶原蛋白;它们对α - 平滑肌肌动蛋白和巢蛋白的阳性反应较弱,而上皮细胞角蛋白呈阴性。在适当的诱导条件下培养时,这两种细胞类型都可以沿脂肪生成和成骨谱系分化。此外,成纤维细胞样间充质干细胞表现出高增殖潜能。这些发现尤为重要,因为在再生医学中,皮肤或脂肪组织易于获取用于自体细胞移植。总之,这些数据表明,具有多系分化潜能的真皮成纤维细胞存在于人类真皮中,它们可能在皮肤伤口愈合中起关键作用。

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