VALIDATION OF A MICROGEL-BASED IN VITRO 3D BONE MARROW MODEL FOR MULTIPLE MYELOMA

• Published in: International journal of artificial organs 2023-07, Vol.46 (7), p.432
• Main Authors: García-Briega, M I, Plá–Salom, J, Clara–Trujillo, S, Ródenas–Rochina, J, Cordón, L, Sempere, A, Gómez, Ribelles J L
• Format: Article
• Language: English
• Subjects: Apoptosis; Biomimetics; Biomolecules; Bone marrow; Cell culture; Cell cycle; Cell growth; Cell proliferation; Dextran; Dextrans; Drug development; Drug resistance; Extracellular matrix; Hyaluronic acid; Malignancy; Mesenchymal stem cells; Microgels; Microspheres; Multiple myeloma; Physicochemical properties; Plasma cells; Stem cells; Three dimensional models
• ISSN: 0391-3988; 1724-6040

Objectives: Multiple myeloma (MM) is a haematological malignancy involving monoclonal plasma cells within the bone marrow (BM). Interactions between MM cells and the BM niche significantly affect MM development and drug resistance. We aimed to develop a biomimetic 3D platform to study MM behaviour. We included commercial dextran microspheres (Cytodex 1) functionalised with extracellular matrix (ECM) biomolecules. As the cellular component of the BM niche, we co-cultured MM cells and human mesenchymal stem cells (hMSCs). Methods: Layer-by-Layer (LbL) technique was used to functionalise microspheres with heparan and chondroitin sulphate, hyaluronic acid and collagen. The morphological and physicochemical properties of the coatings were assessed. Cell culture was carried out in suspension and lasted up to three days. We used three MM cell lines (RPMI8226, MM1S and U226) in co-culture with hMSCs, introduced in the model as an agglomerate of cells and non-functionalised microspheres. Cell cycle distribution, apoptosis and proliferation assays were assessed to validate the culture platform and to study co-culture interactions. Results: We confirmed the presence of the biomolecules on the microspheres' surface. Good cell proliferation was obtained in all the conditions and MM cell lines, RPMI8226 being the one with the highest cell growth. Apoptosis and cell cycle assays showed that culture conditions affect the viability and percentage of active cells in the RPMI8226 cell line. Regarding the U226 cell line, viability was barely affected; but the rate of active cells increased significantly. Conclusions: Microsphere characterisation demonstrated the LbL technique is suitable for functionalising Cytodex 1 with biomolecules of the BM ECM. Our platform allows the growth of all three MM cell lines. Future research will address using this model as a study platform for selecting and evaluating new drugs against MM, which could improve response and personalised therapy for this disease.