Alpha10 integrin expression is up-regulated on fibroblast growth factor-2-treated mesenchymal stem cells with improved chondrogenic differentiation potential.

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 alpha10 and alpha11 of the collagen binding integrins alpha10beta1 and alpha11beta1 are expressed by human MSCs in monolayer cultures. We also demonstrate that the expression of alpha10 increases, while alpha1 and alpha11 decrease, during aggregate culture of MSCs in chondrogenic medium. Alpha10beta1 is expressed by chondrocytes in cartilage, whereas alpha11beta1 integrins are predominantly expressed by subsets of the fibroblastic lineage. In extensive monolayer cultures of MSCs, alpha10 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 alpha10 expression, but also in decreased alpha11 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 alpha10 expression. We also demonstrate expression of alpha10 and alpha11 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 alpha10 positive and propose alpha10 as a potential marker to predict the differentiation state of MSCs.

Mesenchymal progenitor cell-mediated inhibition of tumor growth in vivo and in vitro in gelatin matrix.

A preformed gelatin matrix containing adherent rat colon carcinoma cells was transplanted subcutaneously into rats to analyze the outgrowth of the tumor and the inflammatory response. The gelatin matrix simplifies the precise localization of the tumor cells early after implantation and allows the gelatin piece with a growing tumor to be dissected for analysis in vitro, after various times in vivo. The immortalized mesenchymal progenitor cell line MPC1cE was cocultured with rat colon carcinoma cells in vivo in gelatin matrix. The mesenchymal progenitor cells inhibited the outgrowth of the rat colon carcinoma and a complete inhibition was seen if the number of mesenchymal progenitor cells were at least equal to the number of tumor cells. The mixture of tumor cells and mesenchymal progenitor cells induced more infiltration of monocytes and granulocytes than tumor cells or mesenchymal progenitor cells alone. Infiltration of T cells and CD31+ endothelial cells correlated to the presence of tumor cells and not to mesenchymal progenitor cells. These findings suggest that tumor cell culture in vivo in a gelatin matrix is effective for early localization of tumor cells in vivo and that mesenchymal progenitor cells effectively inhibit the growth of the tumor cells in vivo.