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Cost-Effective Mechanical Aggregation of Cardiac Progenitors and Encapsulation in Matrigel Support Self-Organization in a Dynamic Culture Environment

Human iPSC-derived self-organized cardiac tissues can be valuable for the development of platforms for disease modeling and drug screening, enhancing test accuracy and reducing pharmaceutical industry financial burden. However, current differentiation systems still rely on static culture conditions...

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Autores principales: Dias, Tiago P., Pinto, Sandra N., Carvalho, Sandra, Fernandes, Tiago G., Fernandes, Fábio, Diogo, Maria Margarida, Peleteiro, Maria C., Prieto, Manuel, Cabral, Joaquim M. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779514/
https://www.ncbi.nlm.nih.gov/pubmed/36555427
http://dx.doi.org/10.3390/ijms232415785
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author Dias, Tiago P.
Pinto, Sandra N.
Carvalho, Sandra
Fernandes, Tiago G.
Fernandes, Fábio
Diogo, Maria Margarida
Peleteiro, Maria C.
Prieto, Manuel
Cabral, Joaquim M. S.
author_facet Dias, Tiago P.
Pinto, Sandra N.
Carvalho, Sandra
Fernandes, Tiago G.
Fernandes, Fábio
Diogo, Maria Margarida
Peleteiro, Maria C.
Prieto, Manuel
Cabral, Joaquim M. S.
author_sort Dias, Tiago P.
collection PubMed
description Human iPSC-derived self-organized cardiac tissues can be valuable for the development of platforms for disease modeling and drug screening, enhancing test accuracy and reducing pharmaceutical industry financial burden. However, current differentiation systems still rely on static culture conditions and specialized commercial microwells for aggregation, which hinders the full potential of hiPSC-derived cardiac tissues. Herein, we integrate cost-effective and reproducible manual aggregation of hiPSC-derived cardiac progenitors with Matrigel encapsulation and a dynamic culture to support hiPSC cardiac differentiation and self-organization. Manual aggregation at day 7 of cardiac differentiation resulted in 97% of beating aggregates with 78% of cTnT-positive cells. Matrigel encapsulation conjugated with a dynamic culture promoted cell migration and the creation of organized structures, with observed cell polarization and the creation of lumens. In addition, encapsulation increased buoyancy and decreased coalescence of the hiPSC-derived cardiac aggregates. Moreover, VEGF supplementation increased over two-fold the percentage of CD31-positive cells resulting in the emergence of microvessel-like structures. Thus, this study shows that the explored culture parameters support the self-organization of hiPSC-derived cardiac microtissues containing multiple cardiac cell types. Additional stimuli (e.g., BMP) in long-term scalable and fully automatized cultures can further potentiate highly structured and mature hiPSC-derived cardiac models, contributing to the development of reliable platforms for high-throughput drug screening and disease modeling.
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spelling pubmed-97795142022-12-23 Cost-Effective Mechanical Aggregation of Cardiac Progenitors and Encapsulation in Matrigel Support Self-Organization in a Dynamic Culture Environment Dias, Tiago P. Pinto, Sandra N. Carvalho, Sandra Fernandes, Tiago G. Fernandes, Fábio Diogo, Maria Margarida Peleteiro, Maria C. Prieto, Manuel Cabral, Joaquim M. S. Int J Mol Sci Article Human iPSC-derived self-organized cardiac tissues can be valuable for the development of platforms for disease modeling and drug screening, enhancing test accuracy and reducing pharmaceutical industry financial burden. However, current differentiation systems still rely on static culture conditions and specialized commercial microwells for aggregation, which hinders the full potential of hiPSC-derived cardiac tissues. Herein, we integrate cost-effective and reproducible manual aggregation of hiPSC-derived cardiac progenitors with Matrigel encapsulation and a dynamic culture to support hiPSC cardiac differentiation and self-organization. Manual aggregation at day 7 of cardiac differentiation resulted in 97% of beating aggregates with 78% of cTnT-positive cells. Matrigel encapsulation conjugated with a dynamic culture promoted cell migration and the creation of organized structures, with observed cell polarization and the creation of lumens. In addition, encapsulation increased buoyancy and decreased coalescence of the hiPSC-derived cardiac aggregates. Moreover, VEGF supplementation increased over two-fold the percentage of CD31-positive cells resulting in the emergence of microvessel-like structures. Thus, this study shows that the explored culture parameters support the self-organization of hiPSC-derived cardiac microtissues containing multiple cardiac cell types. Additional stimuli (e.g., BMP) in long-term scalable and fully automatized cultures can further potentiate highly structured and mature hiPSC-derived cardiac models, contributing to the development of reliable platforms for high-throughput drug screening and disease modeling. MDPI 2022-12-13 /pmc/articles/PMC9779514/ /pubmed/36555427 http://dx.doi.org/10.3390/ijms232415785 Text en © 2022 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
Dias, Tiago P.
Pinto, Sandra N.
Carvalho, Sandra
Fernandes, Tiago G.
Fernandes, Fábio
Diogo, Maria Margarida
Peleteiro, Maria C.
Prieto, Manuel
Cabral, Joaquim M. S.
Cost-Effective Mechanical Aggregation of Cardiac Progenitors and Encapsulation in Matrigel Support Self-Organization in a Dynamic Culture Environment
title Cost-Effective Mechanical Aggregation of Cardiac Progenitors and Encapsulation in Matrigel Support Self-Organization in a Dynamic Culture Environment
title_full Cost-Effective Mechanical Aggregation of Cardiac Progenitors and Encapsulation in Matrigel Support Self-Organization in a Dynamic Culture Environment
title_fullStr Cost-Effective Mechanical Aggregation of Cardiac Progenitors and Encapsulation in Matrigel Support Self-Organization in a Dynamic Culture Environment
title_full_unstemmed Cost-Effective Mechanical Aggregation of Cardiac Progenitors and Encapsulation in Matrigel Support Self-Organization in a Dynamic Culture Environment
title_short Cost-Effective Mechanical Aggregation of Cardiac Progenitors and Encapsulation in Matrigel Support Self-Organization in a Dynamic Culture Environment
title_sort cost-effective mechanical aggregation of cardiac progenitors and encapsulation in matrigel support self-organization in a dynamic culture environment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779514/
https://www.ncbi.nlm.nih.gov/pubmed/36555427
http://dx.doi.org/10.3390/ijms232415785
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