Toward a Microencapsulated 3D hiPSC-Derived in vitro Cardiac Microtissue for Recapitulation of Human Heart Microenvironment Features

Detalhes bibliográficos
Autor(a) principal: Abecasis, Bernardo
Data de Publicação: 2020
Outros Autores: Canhão, Pedro G. M., Almeida, Henrique V., Calmeiro, Tomás, Fortunato, Elvira, Gomes-Alves, Patrícia, Serra, Margarida, Alves, Paula M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/117343
Resumo: SAICTPAC/0047/2015 PTDC/BTMSAL/32566/ 2017 PTDC/MEC-CAR/29590/2017 UIDB/04462/2020 UIDP/04462/2020 H2020, ID:874827 SFRH/BD/52475/2013 SFRH/BPD/120595/2016
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spelling Toward a Microencapsulated 3D hiPSC-Derived in vitro Cardiac Microtissue for Recapitulation of Human Heart Microenvironment Features3D culturecardiomyocytesendothelial cellsengineered cardiac tissuesfibroblastshiPSCmicroencapsulationBiotechnologyBioengineeringHistologyBiomedical EngineeringSDG 3 - Good Health and Well-beingSAICTPAC/0047/2015 PTDC/BTMSAL/32566/ 2017 PTDC/MEC-CAR/29590/2017 UIDB/04462/2020 UIDP/04462/2020 H2020, ID:874827 SFRH/BD/52475/2013 SFRH/BPD/120595/2016The combination of cardiomyocytes (CM) and non-myocyte cardiac populations, such as endothelial cells (EC), and mesenchymal cells (MC), has been shown to be critical for recapitulation of the human heart tissue for in vitro cell-based modeling. However, most of the current engineered cardiac microtissues still rely on either (i) murine/human limited primary cell sources, (ii) animal-derived and undefined hydrogels/matrices with batch-to-batch variability, or (iii) culture systems with low compliance with pharmacological high-throughput screenings. In this work, we explored a culture platform based on alginate microencapsulation and suspension culture systems to develop three-dimensional (3D) human cardiac microtissues, which entails the co-culture of human induced pluripotent stem cell (hiPSC) cardiac derivatives including aggregates of hiPSC–CM and single cells of hiPSC–derived EC and MC (hiPSC–EC+MC). We demonstrate that the 3D human cardiac microtissues can be cultured for 15 days in dynamic conditions while maintaining the viability and phenotype of all cell populations. Noteworthy, we show that hiPSC–EC+MC survival was promoted by the co-culture with hiPSC–CM as compared to the control single-cell culture. Additionally, the presence of the hiPSC–EC+MC induced changes in the physical properties of the biomaterial, as observed by an increase in the elastic modulus of the cardiac microtissue when compared to the hiPSC–CM control culture. Detailed characterization of the 3D cardiac microtissues revealed that the crosstalk between hiPSC–CM, hiPSC–EC+MC, and extracellular matrix induced the maturation of hiPSC–CM. The cardiac microtissues displayed functional calcium signaling and respond to known cardiotoxins in a dose-dependent manner. This study is a step forward on the development of novel 3D cardiac microtissues that recapitulate features of the human cardiac microenvironment and is compliant with the larger numbers needed in preclinical research for toxicity assessment and disease modeling.DCM - Departamento de Ciência dos MateriaisCENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N)Instituto de Tecnologia Química e Biológica António Xavier (ITQB)Programme in Translational Medicine (iNOVA4Health)RUNAbecasis, BernardoCanhão, Pedro G. M.Almeida, Henrique V.Calmeiro, TomásFortunato, ElviraGomes-Alves, PatríciaSerra, MargaridaAlves, Paula M.2021-05-07T23:07:37Z2020-11-052020-11-05T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/117343eng2296-4185PURE: 29619338https://doi.org/10.3389/fbioe.2020.580744info: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:RCAAP2024-03-11T05:00:30Zoai:run.unl.pt:10362/117343Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:43:36.332167Repositório 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 Toward a Microencapsulated 3D hiPSC-Derived in vitro Cardiac Microtissue for Recapitulation of Human Heart Microenvironment Features
title Toward a Microencapsulated 3D hiPSC-Derived in vitro Cardiac Microtissue for Recapitulation of Human Heart Microenvironment Features
spellingShingle Toward a Microencapsulated 3D hiPSC-Derived in vitro Cardiac Microtissue for Recapitulation of Human Heart Microenvironment Features
Abecasis, Bernardo
3D culture
cardiomyocytes
endothelial cells
engineered cardiac tissues
fibroblasts
hiPSC
microencapsulation
Biotechnology
Bioengineering
Histology
Biomedical Engineering
SDG 3 - Good Health and Well-being
title_short Toward a Microencapsulated 3D hiPSC-Derived in vitro Cardiac Microtissue for Recapitulation of Human Heart Microenvironment Features
title_full Toward a Microencapsulated 3D hiPSC-Derived in vitro Cardiac Microtissue for Recapitulation of Human Heart Microenvironment Features
title_fullStr Toward a Microencapsulated 3D hiPSC-Derived in vitro Cardiac Microtissue for Recapitulation of Human Heart Microenvironment Features
title_full_unstemmed Toward a Microencapsulated 3D hiPSC-Derived in vitro Cardiac Microtissue for Recapitulation of Human Heart Microenvironment Features
title_sort Toward a Microencapsulated 3D hiPSC-Derived in vitro Cardiac Microtissue for Recapitulation of Human Heart Microenvironment Features
author Abecasis, Bernardo
author_facet Abecasis, Bernardo
Canhão, Pedro G. M.
Almeida, Henrique V.
Calmeiro, Tomás
Fortunato, Elvira
Gomes-Alves, Patrícia
Serra, Margarida
Alves, Paula M.
author_role author
author2 Canhão, Pedro G. M.
Almeida, Henrique V.
Calmeiro, Tomás
Fortunato, Elvira
Gomes-Alves, Patrícia
Serra, Margarida
Alves, Paula M.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv DCM - Departamento de Ciência dos Materiais
CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N)
Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
Programme in Translational Medicine (iNOVA4Health)
RUN
dc.contributor.author.fl_str_mv Abecasis, Bernardo
Canhão, Pedro G. M.
Almeida, Henrique V.
Calmeiro, Tomás
Fortunato, Elvira
Gomes-Alves, Patrícia
Serra, Margarida
Alves, Paula M.
dc.subject.por.fl_str_mv 3D culture
cardiomyocytes
endothelial cells
engineered cardiac tissues
fibroblasts
hiPSC
microencapsulation
Biotechnology
Bioengineering
Histology
Biomedical Engineering
SDG 3 - Good Health and Well-being
topic 3D culture
cardiomyocytes
endothelial cells
engineered cardiac tissues
fibroblasts
hiPSC
microencapsulation
Biotechnology
Bioengineering
Histology
Biomedical Engineering
SDG 3 - Good Health and Well-being
description SAICTPAC/0047/2015 PTDC/BTMSAL/32566/ 2017 PTDC/MEC-CAR/29590/2017 UIDB/04462/2020 UIDP/04462/2020 H2020, ID:874827 SFRH/BD/52475/2013 SFRH/BPD/120595/2016
publishDate 2020
dc.date.none.fl_str_mv 2020-11-05
2020-11-05T00:00:00Z
2021-05-07T23:07:37Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/117343
url http://hdl.handle.net/10362/117343
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2296-4185
PURE: 29619338
https://doi.org/10.3389/fbioe.2020.580744
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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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instacron:RCAAP
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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