Novel microgel culture system as semi-solid three-dimensional in vitro model for the study of multiple myeloma proliferation and drug resistance

Fecha de publicación: 01/04/2022 Fecha Ahead of Print: 17/03/2022

Autores de IIS La Fe

Sandra Clara Trujillo

Autor
Laia Tolosa Pardo

Autor
Lourdes Cordón Gallego

Autor
Amparo Sempere Talens

Autor
Gloria Gallego Ferrer

Autor
Jose Luis Gomez Ribelles

Autor

Grupos

Hematología y Hemoterapia

Investigador Principal

Javier De La Rubia Comos
Hepatología experimental y Trasplante hepático

Investigador Principal

Laia Tolosa Pardo

Abstract

Multiple myeloma (MM) is a hematological malignancy in which the patient's drug resistance is one of the main clinical problems. As 2D cultures do not recapitulate the cellular microenvironment, which has a key role in drug resistance, there is an urgent need for better biomimetic models. Here, a novel 3D platform is used to model MM. The semi-solid culture consists of a dynamic suspension of microspheres and MM cells, termed as microgel. Microspheres are synthesized with acrylic polymers of different sizes, compositions, and functionalities (fibronectin or hyaluronic acid). Optimal conditions for the platform in terms of agitation speed and microsphere size have been determined. With these parameters the system allows good proliferation of the MM cell lines RPMI8226, U226, and MM1.S. Interestingly, when used for drug resistance studies, culture of the three MM cell lines in microgels showed close agreement in revealing the role of acrylic acid in resistance to anti-MM drugs such as dexamethasone and bortezomib. This work presents a unique platform for the in vitro modeling of non-solid tumors since it allows keeping non-adherent cells in suspension conditions but in a 3D context that can be easily tuned with different functionalizations.

Datos de la publicación

ISSN/ISSNe:: 2772-9508, 2772-9508
Tipo:: Article
Páginas:: 212749-212749
DOI:: 10.1016/j.bioadv.2022.212749

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Filiaciones

Clara-Trujillo S:: Centre for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, Valencia 46022, Spain

Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valencia 46022, Spain
Tolosa L:: Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valencia 46022, Spain

Instituto de Investigación. Experimental Hepatology Unit, Health Research Institute La Fe (IIS La Fe), Valencia 46026, Spain
Cordón L:: Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Carlos III, Madrid, Spain

Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
Sempere A:: Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Carlos III, Madrid, Spain

Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Gallego Ferrer G:: Centre for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, Valencia 46022, Spain

Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valencia 46022, Spain
Gómez Ribelles JL:: Centre for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, Valencia 46022, Spain

Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valencia 46022, Spain