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Multiple myeloma is characterized by the clonal proliferation of malignant plasma cells in the bone marrow microenvironment. The pathogenesis consists, in part, in critical interactions between myeloma cells and the mesenchymal stem cells (MSC). The interactions between myeloma cells and bone marrow cells are establish through surface receptors (e.g. integrins, cell adhesion molecules, etc.), which determine tumor growth, survival, migration and drug resistance. Mesenchymal stromal cells modulate the pattern of myeloma markers on the cellular surface in vitro towards a less differentiated phenotype. However, the exact mechanism by which mesenchymal stromal cells carry out their functions is not yet fully understood.

To evaluate the effect of MSCs from healthy donors and myeloma patients over malignant plasma cells and the molecular changes produced for the interaction each other.

Interactions between both cell types were studied through different co-cultures studies. We evaluate differences between culturing primary MSC cells and MM cell line RPMi 8226. Pathological MSCs were extracted from the bone marrow of newly diagnose MM patients. On the other hand, purified healthy MSCs will be isolated from donor patients. Pathological or healthy MSCs were cultured and co-cultured 24h after seeding with MM plasma cells RPMI 8226 for duplicates at 24, 48 and 72h. The phenotypical and molecular effect of the interaction of both cells were characterized by viability through trypan blue, cell apoptosis percentage (7AAD) and variations on expression of cell surface proteins (MSCs: CD90, CD105, CD106 and CD54. MM cell: CD138, CD38, CD49d and CD11a) using flow cytometry, and statistically analyzed with GraphPad.

As reported in literature CD106 expression increase when MSCs are co-cultured with plasma cells. Adhesion of tumor cells to BMSC activates many pathways resulting in upregulation of cell cycle and anti-apoptotic proteins. MM pathophysiology is supported by a strong interaction between CD106/CD49d.

Changes in VCAM-1 and VLA-4 expression have been demonstrated in cell lines assays, and were corroborated with primary cells in the context of MSCs protection over MM plasma cell. Thus, MM pathological MSCs did not change VCAM-1 levels and MM plasma cell protection be held. However, healthy MSCs have the capacity to modulate the VCAM-1 in mid-term to avoid the protection effect. Therefore, these results suggest MSCs VCAM-1 as potential drug therapy target in MM disease.