Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2019 |
| 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/1822/67367 |
Resumo: | Author Manuscript |
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Engineering of human cardiac muscle electromechanically matured to an adult-like phenotypeCell Culture TechniquesCell DifferentiationHeartHumansInduced Pluripotent Stem CellsMyocytes, CardiacTissue EngineeringMyocardiumHuman induced pluripotent stem cellsCardiomyocytes3D TissueElectromechanical stimulationMaturationCiências Médicas::Medicina BásicaScience & TechnologyAuthor ManuscriptThe application of tissue-engineering approaches to human induced pluripotent stem (hiPS) cells enables the development of physiologically relevant human tissue models for in vitro studies of development, regeneration, and disease. However, the immature phenotype of hiPS-derived cardiomyocytes (hiPS-CMs) limits their utility. We have developed a protocol to generate engineered cardiac tissues from hiPS cells and electromechanically mature them toward an adult-like phenotype. This protocol also provides optimized methods for analyzing these tissues' functionality, ultrastructure, and cellular properties. The approach relies on biological adaptation of cultured tissues subjected to biomimetic cues, applied at an increasing intensity, to drive accelerated maturation. hiPS cells are differentiated into cardiomyocytes and used immediately after the first contractions are observed, when they still have developmental plasticity. This starting cell population is combined with human dermal fibroblasts, encapsulated in a fibrin hydrogel and allowed to compact under passive tension in a custom-designed bioreactor. After 7 d of tissue formation, the engineered tissues are matured for an additional 21 d by increasingly intense electromechanical stimulation. Tissue properties can be evaluated by measuring contractile function, responsiveness to electrical stimuli, ultrastructure properties (sarcomere length, mitochondrial density, networks of transverse tubules), force-frequency and force-length relationships, calcium handling, and responses to β-adrenergic agonists. Cell properties can be evaluated by monitoring gene/protein expression, oxidative metabolism, and electrophysiology. The protocol takes 4 weeks and requires experience in advanced cell culture and machining methods for bioreactor fabrication. We anticipate that this protocol will improve modeling of cardiac diseases and testing of drugs.NIBIB and NCATS grant EB17103 (G.V.-N.); NIBIB, NCATS, NIAMS, NIDCR, and NIEHS grant EB025765 (G.V.-N.); NHLBI grants HL076485 (G.V.-N.) and HL138486 (M.Y.); NSF grant 16478 (G.V.-N.); the University of Minho MD/PhD program (D.T.); a Japan Society for the Promotion of Science fellowship (K.M.); and the Columbia University Stem Cell Initiative (L.S., M.Y.)Nature ResearchUniversidade do MinhoRonaldson-Bouchard, KaceyYeager, KeithTeles, DiogoChen, TimothyMa, StephenSong, LouJinMorikawa, KumiWobma, Holly M.Ruiz, Edward C.Yazawa, MasayukiVunjak-Novakovic, Gordana2019-092019-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/67367engRonaldson-Bouchard, K., Yeager, K., Teles, D., et. al. (2019). Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype. Nature protocols, 14(10), 2781-28171754-21891750-279910.1038/s41596-019-0189-831492957https://www.nature.com/articles/s41596-019-0189-8info: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:RCAAP2023-07-21T12:21:49Zoai:repositorium.sdum.uminho.pt:1822/67367Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:15:11.456105Repositório 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 |
Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype |
| title |
Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype |
| spellingShingle |
Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype Ronaldson-Bouchard, Kacey Cell Culture Techniques Cell Differentiation Heart Humans Induced Pluripotent Stem Cells Myocytes, Cardiac Tissue Engineering Myocardium Human induced pluripotent stem cells Cardiomyocytes 3D Tissue Electromechanical stimulation Maturation Ciências Médicas::Medicina Básica Science & Technology |
| title_short |
Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype |
| title_full |
Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype |
| title_fullStr |
Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype |
| title_full_unstemmed |
Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype |
| title_sort |
Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype |
| author |
Ronaldson-Bouchard, Kacey |
| author_facet |
Ronaldson-Bouchard, Kacey Yeager, Keith Teles, Diogo Chen, Timothy Ma, Stephen Song, LouJin Morikawa, Kumi Wobma, Holly M. Ruiz, Edward C. Yazawa, Masayuki Vunjak-Novakovic, Gordana |
| author_role |
author |
| author2 |
Yeager, Keith Teles, Diogo Chen, Timothy Ma, Stephen Song, LouJin Morikawa, Kumi Wobma, Holly M. Ruiz, Edward C. Yazawa, Masayuki Vunjak-Novakovic, Gordana |
| author2_role |
author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidade do Minho |
| dc.contributor.author.fl_str_mv |
Ronaldson-Bouchard, Kacey Yeager, Keith Teles, Diogo Chen, Timothy Ma, Stephen Song, LouJin Morikawa, Kumi Wobma, Holly M. Ruiz, Edward C. Yazawa, Masayuki Vunjak-Novakovic, Gordana |
| dc.subject.por.fl_str_mv |
Cell Culture Techniques Cell Differentiation Heart Humans Induced Pluripotent Stem Cells Myocytes, Cardiac Tissue Engineering Myocardium Human induced pluripotent stem cells Cardiomyocytes 3D Tissue Electromechanical stimulation Maturation Ciências Médicas::Medicina Básica Science & Technology |
| topic |
Cell Culture Techniques Cell Differentiation Heart Humans Induced Pluripotent Stem Cells Myocytes, Cardiac Tissue Engineering Myocardium Human induced pluripotent stem cells Cardiomyocytes 3D Tissue Electromechanical stimulation Maturation Ciências Médicas::Medicina Básica Science & Technology |
| description |
Author Manuscript |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019-09 2019-09-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/67367 |
| url |
http://hdl.handle.net/1822/67367 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Ronaldson-Bouchard, K., Yeager, K., Teles, D., et. al. (2019). Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype. Nature protocols, 14(10), 2781-2817 1754-2189 1750-2799 10.1038/s41596-019-0189-8 31492957 https://www.nature.com/articles/s41596-019-0189-8 |
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info:eu-repo/semantics/openAccess |
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openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Nature Research |
| publisher.none.fl_str_mv |
Nature Research |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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