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α10 integrin expression is up-regulated on fibroblast growth factor-2-treated mesenchymal stem cells with improved chondrogenic differentiation potential

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STEM CELLS AND DEVELOPMENT
卷 16, 期 6, 页码 965-978

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MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2007.0049

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Mesenchymal stem cells (MSCs) are multipotent cells that have the capacity to differentiate into various different cell lineages and can generate bone, cartilage and adipose tissue. MSCs are presently characterized using a broad range of different cell-surface markers that are not exclusive to MSCs and not sensitive to culture conditions or differentiation capacity. We show that the integrin subunits alpha 10 and all of the collagen binding integrins alpha 10 beta 1 and alpha 11 beta 1 are expressed by human MSCs in monolayer cultures. We also demonstrate that the expression of alpha 10 increases, while alpha 10 beta 1 and all decrease, during aggregate culture of MSCs in chondrogenic medium. alpha 10 beta 1 is expressed by chondrocytes in cartilage, whereas alpha 11 beta 1 integrins are predominantly expressed by subsets of the fibroblastic lineage. In extensive monolayer cultures of MSCs, alpha 10 expression is down-regulated. We show that this down-regulation is reversed by fibroblast growth factor-2 (FGF-2) treatment. Addition of FGF-2 to MSCs not only results in increased alpha 10 expression, but also in decreased all expression. FGF-2 treatment of MSCs has been shown to keep the cells more multipotent and also induces cell proliferation and Sox-9 up-regulation. We demonstrate improved chondrogenecity as well as increased collagen-dependant migratory potential of FGF-2-treated MSCs having a high alpha 10 expression. We also demonstrate expression of alpha 10 and all integrin subunits in the endosteum and periosteum of mice, but very low or not detectable expression levels in freshly aspired human or mouse BM. We show that MSCs with high chondrogenic differentiation potential are highly alpha 10 positive and propose alpha 10 as a potential marker to predict the differentiation state of MSCs.

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