3D Models of Surrogate Multiple Myeloma Bone Marrow Microenvironments: Insights on Disease Pathophysiology and Patient-Specific Response to Drugs

Abstract

Multiple Myeloma (MM) develops almost exclusively within the Bone Marrow (BM), highlighting the critical role of the microenvironment in conditioning disease progression and resistance to drugs. Indeed, while the therapeutic armamentarium for MM has significantly improved over the past 20 years, the disease remains ultimately incurable. This failure may depend on the high phenotypic and genetic heterogeneity of MM, but also on the paucity and inadequacy of two-dimensional (2D) conventional preclinical models in reproducing MM within the BM. In the present paper, we provide a brief updated overview on MM BM microenvironment. We then discuss newly developed preclinical models mimicking MM/microenvironment interactions, including three-dimensional (3D), gel-based, in vitro models and a novel ex vivo system of isolated tumor and stromal cells cultured in bioreactor. Potential applications of each model, relative to investigation of MM pathogenic mechanisms and prediction of the best drug/combination for each individual patient will be also evaluated. Keywords: multiple myeloma, tumor microenvironment, 2D/3D culture models, 3D culture in bioreactor, drug testing, personalized therapy