BUSCADOR RECOLECTA

The development of three-dimensional environments to mimic the in vivo cellular response is a problem in the building of disease models. This study aimed to synthesize and validate three-dimensional support for culturing monoclonal plasma cells (mPCs) as a disease model for multiple myeloma. The three-dimensional environment is a biomimetic microgel formed by alginate microspheres and produced on a microfluidic device whose surface has been functionalized by a layer-by-layer process with components of the bone marrow’s extracellular matrix, which will interact with mPC. As a proof of concept, RPMI 8226 cell line cells were cultured in our 3D culture platform. We proved that hyaluronic acid significantly increased cell proliferation and corroborated its role in inducing resistance to dexamethasone. Despite collagen type I having no effect on proliferation, it generated significant resistance to dexamethasone. Additionally, it was evidenced that both biomolecules were unable to induce resistance to bortezomib. These results validate the functionalized microgels as a 3D culture system that emulates the interaction between tumoral cells and the bone marrow extracellular matrix. This 3D environment could be a valuable culture system to test antitumoral drugs efficiency in multiple myeloma.

Multiple myeloma is a hematologic neoplasm caused by an uncontrolled clonal proliferation of neoplastic plasma cells (nPCs) in the bone marrow. The development and survival of this disease is tightly related to the bone marrow environment. Proliferation and viability of nPCs depend on their interaction with the stromal cells and the extracellular matrix components, which also influences the appearance of drug resistance. Recapitulating these interactions in an in vitro culture requires 3D environments that incorporate the biomolecules of interest. In this work, we studied the proliferation and viability of three multiple myeloma cell lines in a microgel consisting of biostable microspheres with fibronectin (FN) on their surfaces. We also showed that the interaction of the RPMI8226 cell line with FN induced cell arrest in the G0/G1 cell cycle phase. RPMI8226 cells developed a significant resistance to dexamethasone, which was reduced when they were treated with dexamethasone and bortezomib in combination., CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008–2011, Iniciativa Ingenio 2010, and Consolider Program. CIBER Actions were financed by the Instituto de Salud Carlos III, with assistance from the European Regional Development Fund. The kind supplying of RPMI 8226 cells by Beatriz Martin (Josep Carreras Leukaemia Research Institute) is greatly acknowledged. The Microscopy Service of the UPV (Universitat Politècnica de València) is gratefully acknowledged.