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Biomimetic 3D Environment Based on Microgels as a Model for the Generation of Drug Resistance in Multiple Myeloma

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 thr...

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Autores principales: Marín-Payá, Juan Carlos, Díaz-Benito, Blanca, Martins, Luis Amaro, Trujillo, Sandra Clara, Cordón, Lourdes, Lanceros-Méndez, Senentxu, Gallego Ferrer, Gloria, Sempere, Amparo, Gómez Ribelles, José Luis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658353/
https://www.ncbi.nlm.nih.gov/pubmed/34885273
http://dx.doi.org/10.3390/ma14237121
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author Marín-Payá, Juan Carlos
Díaz-Benito, Blanca
Martins, Luis Amaro
Trujillo, Sandra Clara
Cordón, Lourdes
Lanceros-Méndez, Senentxu
Gallego Ferrer, Gloria
Sempere, Amparo
Gómez Ribelles, José Luis
author_facet Marín-Payá, Juan Carlos
Díaz-Benito, Blanca
Martins, Luis Amaro
Trujillo, Sandra Clara
Cordón, Lourdes
Lanceros-Méndez, Senentxu
Gallego Ferrer, Gloria
Sempere, Amparo
Gómez Ribelles, José Luis
author_sort Marín-Payá, Juan Carlos
collection PubMed
description 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.
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spelling pubmed-86583532021-12-10 Biomimetic 3D Environment Based on Microgels as a Model for the Generation of Drug Resistance in Multiple Myeloma Marín-Payá, Juan Carlos Díaz-Benito, Blanca Martins, Luis Amaro Trujillo, Sandra Clara Cordón, Lourdes Lanceros-Méndez, Senentxu Gallego Ferrer, Gloria Sempere, Amparo Gómez Ribelles, José Luis Materials (Basel) Article 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. MDPI 2021-11-23 /pmc/articles/PMC8658353/ /pubmed/34885273 http://dx.doi.org/10.3390/ma14237121 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Marín-Payá, Juan Carlos
Díaz-Benito, Blanca
Martins, Luis Amaro
Trujillo, Sandra Clara
Cordón, Lourdes
Lanceros-Méndez, Senentxu
Gallego Ferrer, Gloria
Sempere, Amparo
Gómez Ribelles, José Luis
Biomimetic 3D Environment Based on Microgels as a Model for the Generation of Drug Resistance in Multiple Myeloma
title Biomimetic 3D Environment Based on Microgels as a Model for the Generation of Drug Resistance in Multiple Myeloma
title_full Biomimetic 3D Environment Based on Microgels as a Model for the Generation of Drug Resistance in Multiple Myeloma
title_fullStr Biomimetic 3D Environment Based on Microgels as a Model for the Generation of Drug Resistance in Multiple Myeloma
title_full_unstemmed Biomimetic 3D Environment Based on Microgels as a Model for the Generation of Drug Resistance in Multiple Myeloma
title_short Biomimetic 3D Environment Based on Microgels as a Model for the Generation of Drug Resistance in Multiple Myeloma
title_sort biomimetic 3d environment based on microgels as a model for the generation of drug resistance in multiple myeloma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658353/
https://www.ncbi.nlm.nih.gov/pubmed/34885273
http://dx.doi.org/10.3390/ma14237121
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