Toward a Microencapsulated 3D hiPSC-Derived in vitro Cardiac Microtissue for Recapitulation of Human Heart Microenvironment Features
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , |
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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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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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) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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 |
repository.mail.fl_str_mv |
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1799138045367156736 |