Description:
Matrix remodeling could be an important mode of action of multipotent mesenchymalstromal cells (MSC) in extracellular matrix (ECM) disease, but knowledge is limited in this respect.As MSC are well-known to adapt their behavior to their environment, we aimed to investigateif their mode of action would change in response to healthy versus pathologically altered ECM.Human MSC-derived ECM was produced under different culture conditions, including standardculture, culture on Matrigel-coated dishes, and stimulation with the pro-fibrotic transforming growthfactor-1 (TGF1). The MSC-ECM was decellularized, characterized by histochemistry, and usedas MSC culture substrate reflecting different ECM conditions. MSC were cultured on the differentECM substrates or in control conditions for 2 days. Culture on ECM increased the presence of surfacemolecules with ECM receptor function in the MSC, demonstrating an interaction between MSCand ECM. In MSC cultured on Matrigel-ECM and TGF1-ECM, which displayed a fibrosis-likemorphology, gene expression of collagens and decorin, as well as total matrix metalloproteinase(MMP) activity in the supernatant were decreased as compared with control conditions. Theseresults demonstrated that MSC adapt to their ECM environment, which may include pathologicaladaptations that could compromise therapeutic efficacy.