3D biomimetic microgel platform for multiple myeloma: Approaching tumor microenvironment on cell lines and...

This work aimed to develop and characterize a three-dimensional culture platform that recreates the tumor microenvironment of multiple myeloma cells (MMCs), focusing on how atypical plasma cells (aPCs) interact with other bone marrow cells and extracellular matrix (ECM) components to develop drug resistance. The biomimetic platform consists of a static system based on a conical agarose geometry that facilitates the agglomeration and proliferation of aPCs. Magnetic alginate microgels, manufactured by microfluidics, configure the ECM through a layer-by-layer functionalization with collagen, hyaluronic acid, chondroitin sulfate, and heparin. In addition, bone marrow mesenchymal stem cell (BMMSC) pellets were integrated to simulate direct and indirect interactions between BMMSCs and MMCs. The platform has been validated with three lines of MMCs (RPMI8226, MM1S, U266) and the patients' mononuclear cell fraction collected from bone marrow aspirates extracted in two Spanish Hospitals. The microgel analysis aimed to verify stability and to characterize the presence of the different coatings. Biological studies have investigated the proliferation and resistance to drug treatments in MM cell lines. In addition, patient-derived cells were cultured for up to 14 days to study the survival and possible immunophenotypic changes of the atypical plasma cell (aPC) fraction.