A unique three-dimensional SCID-polymeric scaffold (SCID-synth-hu) model for in vivo expansion of human primary multiple myeloma cells

Multiple myeloma (MM) cells home to the bone marrow (BM) and adhere to extracellular matrix (ECM) proteins and to bone marrow stromal cells (BMSCs). The close cross talk between MM cells and cells of the non-tumor compartment within the BM has a key role in supporting tumor growth, survival and development of drug resistance. This biological scenario has led to a growing interest in novel drugs, targeting MM cells and/or interfering with their human BM milieu (HuBMM). 1 , 2 Based on this, appropriate in vivo models that recapitulate the complex interactions occurring between MM and its HuBMM are required for preclinical evaluation of new anti-MM agents. To date, the in vivo study of MM pathobiology and the validation of therapeutic anti-MM agents has been carried out using a variety of models of murine MM or human MM xenografts in immunocompromised mice. 3 These models, however, do not replicate the HuBMM. The development of the SCID (severe combined immunodeficiency)-hu model has been an important advance, as it was the first model to recapitulate a HuBMM in mice. 4 , 5 , 6 However, although the SCID-hu system remains a highly relevant model for preclinical investigation, it does have important limitations: (i) restricted availability of human fetal bone chips; (ii) the allogeneic nature of the fetal BM milieu versus MM cells; and (iii) the significant heterogeneity of implanted human bone chips, collected from different individuals at different gestational age, that may produce experimental variability.