Human Extracellular-Matrix Functionalization of 3D hiPSC-Based Cardiac Tissues Improves Cardiomyocyte Maturation

Detalhes bibliográficos
Autor(a) principal: Almeida, Henrique V.
Data de Publicação: 2021
Outros Autores: Tenreiro, Miguel F., Louro, Ana F., Abecasis, Bernardo, Santinha, Deolinda R., Calmeiro, Tomás, Fortunato, Elvira, Ferreira, Lino, Alves, Paula M., Serra, Margarida
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/125818
Resumo: The work here presented was funded by Fundacao para a Ciencia e Tecnologia (FCT) projects NETDIAMOND (SAICTPAC/0047/2015), financially supported by FEEI-Lisboa2020 and FCT/POCI-01-0145-FEDER-016385, and MetaCardio (PTDC/BTM-SAL/32566/2017); iNOVA4-Health -UIDB/04462/2020 and UIDP/04462/2020, a program financially supported by FCT/Ministerio da Ciencia, Tecnologia e Ensino Superior, through national funds is acknowledged; Funding from INTERFACE Programme, through the Innovation, Technology and Circular Economy Fund (FITEC), is gratefully acknowledged; and EU-funded projects BRAV3 (H2020, ID:874827) and ERAatUC (ref. 669088). HVA, AFL, and DS were financed by FCT Grants SFRH/BPD/120595/2016 and PD/BD/139078/2018 and PD/BD/106051/2015, respectively.
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spelling Human Extracellular-Matrix Functionalization of 3D hiPSC-Based Cardiac Tissues Improves Cardiomyocyte Maturation3D culturecardiac tissue decellularizationcardiomyocyte maturationextracellular matrixhiPSC-CMBiomaterialsChemistry(all)Biomedical EngineeringBiochemistry, medicalSDG 3 - Good Health and Well-beingThe work here presented was funded by Fundacao para a Ciencia e Tecnologia (FCT) projects NETDIAMOND (SAICTPAC/0047/2015), financially supported by FEEI-Lisboa2020 and FCT/POCI-01-0145-FEDER-016385, and MetaCardio (PTDC/BTM-SAL/32566/2017); iNOVA4-Health -UIDB/04462/2020 and UIDP/04462/2020, a program financially supported by FCT/Ministerio da Ciencia, Tecnologia e Ensino Superior, through national funds is acknowledged; Funding from INTERFACE Programme, through the Innovation, Technology and Circular Economy Fund (FITEC), is gratefully acknowledged; and EU-funded projects BRAV3 (H2020, ID:874827) and ERAatUC (ref. 669088). HVA, AFL, and DS were financed by FCT Grants SFRH/BPD/120595/2016 and PD/BD/139078/2018 and PD/BD/106051/2015, respectively.Human induced pluripotent stem cells (hiPSC) possess significant therapeutic potential due to their high self-renewal capability and potential to differentiate into specialized cells such as cardiomyocytes. However, generated hiPSC-derived cardiomyocytes (hiPSC-CM) are still immature, with phenotypic and functional features resembling the fetal rather than their adult counterparts, which limits their application in cell-based therapies, in vitro cardiac disease modeling, and drug cardiotoxicity screening. Recent discoveries have demonstrated the potential of the extracellular matrix (ECM) as a critical regulator in development, homeostasis, and injury of the cardiac microenvironment. Within this context, this work aimed to assess the impact of human cardiac ECM in the phenotype and maturation features of hiPSC-CM. Human ECM was isolated from myocardium tissue through a physical decellularization approach. The cardiac tissue decellularization process reduced DNA content significantly while maintaining ECM composition in terms of sulfated glycosaminoglycans (s-GAG) and collagen content. These ECM particles were successfully incorporated in three-dimensional (3D) hiPSC-CM aggregates (CM+ECM) with no impact on viability and metabolic activity throughout 20 days in 3D culture conditions. Also, CM+ECM aggregates displayed organized and longer sarcomeres, with improved calcium handling when compared to hiPSC-CM aggregates. This study shows that human cardiac ECM functionalization of hiPSC-based cardiac tissues improves cardiomyocyte maturation. The knowledge generated herein provides essential insights to streamline the application of ECM in the development of hiPSC-based therapies targeting cardiac diseases.CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N)DCM - Departamento de Ciência dos MateriaisInstituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNAlmeida, Henrique V.Tenreiro, Miguel F.Louro, Ana F.Abecasis, BernardoSantinha, Deolinda R.Calmeiro, TomásFortunato, ElviraFerreira, LinoAlves, Paula M.Serra, Margarida2021-10-09T04:55:38Z2021-02-152021-02-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/125818eng2576-6422PURE: 28528721https://doi.org/10.1021/acsabm.0c01490info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:06:37Zoai:run.unl.pt:10362/125818Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:45:47.629545Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Human Extracellular-Matrix Functionalization of 3D hiPSC-Based Cardiac Tissues Improves Cardiomyocyte Maturation
title Human Extracellular-Matrix Functionalization of 3D hiPSC-Based Cardiac Tissues Improves Cardiomyocyte Maturation
spellingShingle Human Extracellular-Matrix Functionalization of 3D hiPSC-Based Cardiac Tissues Improves Cardiomyocyte Maturation
Almeida, Henrique V.
3D culture
cardiac tissue decellularization
cardiomyocyte maturation
extracellular matrix
hiPSC-CM
Biomaterials
Chemistry(all)
Biomedical Engineering
Biochemistry, medical
SDG 3 - Good Health and Well-being
title_short Human Extracellular-Matrix Functionalization of 3D hiPSC-Based Cardiac Tissues Improves Cardiomyocyte Maturation
title_full Human Extracellular-Matrix Functionalization of 3D hiPSC-Based Cardiac Tissues Improves Cardiomyocyte Maturation
title_fullStr Human Extracellular-Matrix Functionalization of 3D hiPSC-Based Cardiac Tissues Improves Cardiomyocyte Maturation
title_full_unstemmed Human Extracellular-Matrix Functionalization of 3D hiPSC-Based Cardiac Tissues Improves Cardiomyocyte Maturation
title_sort Human Extracellular-Matrix Functionalization of 3D hiPSC-Based Cardiac Tissues Improves Cardiomyocyte Maturation
author Almeida, Henrique V.
author_facet Almeida, Henrique V.
Tenreiro, Miguel F.
Louro, Ana F.
Abecasis, Bernardo
Santinha, Deolinda R.
Calmeiro, Tomás
Fortunato, Elvira
Ferreira, Lino
Alves, Paula M.
Serra, Margarida
author_role author
author2 Tenreiro, Miguel F.
Louro, Ana F.
Abecasis, Bernardo
Santinha, Deolinda R.
Calmeiro, Tomás
Fortunato, Elvira
Ferreira, Lino
Alves, Paula M.
Serra, Margarida
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N)
DCM - Departamento de Ciência dos Materiais
Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
RUN
dc.contributor.author.fl_str_mv Almeida, Henrique V.
Tenreiro, Miguel F.
Louro, Ana F.
Abecasis, Bernardo
Santinha, Deolinda R.
Calmeiro, Tomás
Fortunato, Elvira
Ferreira, Lino
Alves, Paula M.
Serra, Margarida
dc.subject.por.fl_str_mv 3D culture
cardiac tissue decellularization
cardiomyocyte maturation
extracellular matrix
hiPSC-CM
Biomaterials
Chemistry(all)
Biomedical Engineering
Biochemistry, medical
SDG 3 - Good Health and Well-being
topic 3D culture
cardiac tissue decellularization
cardiomyocyte maturation
extracellular matrix
hiPSC-CM
Biomaterials
Chemistry(all)
Biomedical Engineering
Biochemistry, medical
SDG 3 - Good Health and Well-being
description The work here presented was funded by Fundacao para a Ciencia e Tecnologia (FCT) projects NETDIAMOND (SAICTPAC/0047/2015), financially supported by FEEI-Lisboa2020 and FCT/POCI-01-0145-FEDER-016385, and MetaCardio (PTDC/BTM-SAL/32566/2017); iNOVA4-Health -UIDB/04462/2020 and UIDP/04462/2020, a program financially supported by FCT/Ministerio da Ciencia, Tecnologia e Ensino Superior, through national funds is acknowledged; Funding from INTERFACE Programme, through the Innovation, Technology and Circular Economy Fund (FITEC), is gratefully acknowledged; and EU-funded projects BRAV3 (H2020, ID:874827) and ERAatUC (ref. 669088). HVA, AFL, and DS were financed by FCT Grants SFRH/BPD/120595/2016 and PD/BD/139078/2018 and PD/BD/106051/2015, respectively.
publishDate 2021
dc.date.none.fl_str_mv 2021-10-09T04:55:38Z
2021-02-15
2021-02-15T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/125818
url http://hdl.handle.net/10362/125818
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2576-6422
PURE: 28528721
https://doi.org/10.1021/acsabm.0c01490
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eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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