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Tumor and its embedding microenvironment form a unique, dynamic system, largely orchestrated by cellular players, including fibroblasts and endothelial cells (EC), and surrounding extracellular matrix (ECM) with its distinctive physical, biochemical, and biomechanical properties. There is a general consensus that, beyond genetic mutations and epigenetic modifications, the dialogue that occurs between tumor and its microenvironment, through soluble factors and molecular interactions, may affect tumor cells survival, growth, proliferation, response to chemical/physical factors, and lies the basis for metastatization to distant, specific organs. Accordingly, tight links between tumor and surrounding microenvironment could determine the overall sensitivity to anti-cancer drugs and therefore represent an attractive therapeutic target. Tumor microenvironment plays a critical role also in development and progression of haematological malignancies. In this regard, Multiple Myeloma (MM) represents a paradigmatic condition. The establishment of tight links between MM plasma cells and their microenvironment underlines the need for appropriate models for studying MM biology and predicting the impact of drugs. In the present paper, we briefly summarize the role of BM microenvironment and, particularly, of MM associated angiogenesis, in MM pathogenesis, progression and prognosis. We then provide an overview of the currently available MM models, including animal models and a new three-dimensional (3D), gel-based, in vitro model of human MM microenvironment. Finally, we discuss the potential of RCCS bioreactor-based, dynamic 3D model systems (cell and tissue culture) to investigate critical aspects of human MM pathobiology and possible clinical applications. Advantages and limitations of each model, relative to MM investigation and assessment of drug sensitivity, are also considered

Innovative Models to Assess Multiple Myeloma Biology and the Impact of Drugs