Mesenchymal Stem Cells in Tumor Growth Inhibition and Cartilage Differentiation

Sammanfattning: The work presented in this thesis has been focused on mesenchymal stem cells (MSCs). In the two first studies, the effects of MSCs on tumor growth and development in vitro and in vivo was investigated. In the third study the expression of the integrins alpha10beta1 and alpha11beta1 on MSCs was characterized and the involvement of these two integrins in cartilage development was investigated in vitro. The effect of mesenchymal progenitor cells (MPCs, another name for MSCs) on tumor growth was studied using different tumor models. The tumor cells were co-inoculated with MPCs into rats subcutaneous, intracranial, intrahepatic and retroperitoneal and the results showed an anti-tumor effect induced by the MPCs on both colon carcinoma and glioma. In addition, the interaction between tumor cells and MPCs and the infiltrating cells during the initiation of tumor growth was also investigated. MPCs were co-cultured with H1D2 colon carcinoma cells on gelatin pieces and inserted subcutaneously into rats. The results showed an increase of infiltrating cells such as macrophages and granulocytes in the co-cultures of tumor cells and MSCs. In summary, our results, suggest an anti-tumor effect induced by MPCs. In the third study, the expression of alpha10 and alpha11 integrin subunits was characterized on MSCs and we found that alpha10, in contrast to alpha11 and other markers tested, was down-regulated during culture and that this decrease could be prevented by addition of FGF2 to the MSCs culture. In addition we investigated if alpha10 expression promotes chondrogenic differentiation. In this experiment FGF2 pre-treated MSCs (high alpha10) and untreated MSCs (low alpha10) were subjected to a chondogenic assay. The results showed that the FGF2 pre-treated MSCs had an increased collagen type II and proteoglycan synthesis compared to untreated cells. The results further showed that alpha10 expression was up-regulated and that the expression of alpha11 and collagen type I was down-regulated during chondrogenesis in FGF2 treated MSCs compared to untreated cells. These results may indicate that alpha10 is expressed on multipotent MSCs and/or on cells committed to the chondrogenic lineage.