Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/58497
Título: | Advanced maturation of human cardiac tissue grown from pluripotent stem cells |
Autor(es): | Ronaldson-Bouchard, Kacey Ma, Stephen P. Yeager, Keith Chen, Timothy Song, LouJin Sirabella, Dario Morikawa, Kumi Teles, Diogo Yazawa, Masayuki Vunjak-Novakovic, Gordana |
Palavras-chave: | Adult Calcium Energy Metabolism Heart Humans Induced Pluripotent Stem Cells Isoproterenol Mitochondria Myocardium Myocytes, Cardiac Sarcomeres Transcriptome Cell Differentiation Tissue Culture Techniques |
Data: | Abr-2018 |
Editora: | Nature Research |
Revista: | Nature |
Citação: | Ronaldson-Bouchard, K., Ma, S. P., Yeager, K., et. al. (2018). Advanced maturation of human cardiac tissue grown from pluripotent stem cells. Nature, 556(7700), 239 |
Resumo(s): | Cardiac tissues generated from human induced pluripotent stem cells (iPSCs) can serve as platforms for patient-specific studies of physiology and disease1-6. However, the predictive power of these models is presently limited by the immature state of the cells1, 2, 5, 6. Here we show that this fundamental limitation can be overcome if cardiac tissues are formed from early-stage iPSC-derived cardiomyocytes soon after the initiation of spontaneous contractions and are subjected to physical conditioning with increasing intensity over time. After only four weeks of culture, for all iPSC lines studied, such tissues displayed adult-like gene expression profiles, remarkably organized ultrastructure, physiological sarcomere length (2.2 µm) and density of mitochondria (30%), the presence of transverse tubules, oxidative metabolism, a positive force-frequency relationship and functional calcium handling. Electromechanical properties developed more slowly and did not achieve the stage of maturity seen in adult human myocardium. Tissue maturity was necessary for achieving physiological responses to isoproterenol and recapitulating pathological hypertrophy, supporting the utility of this tissue model for studies of cardiac development and disease. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/58497 |
DOI: | 10.1038/s41586-018-0016-3 |
ISSN: | 0028-0836 |
e-ISSN: | 1476-4687 |
Versão da editora: | https://www.nature.com/articles/s41586-018-0016-3?_ga=2.210913495.338718695.1526860800-1585132472.1526860800 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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teles 2018.pdf | 13,52 MB | Adobe PDF | Ver/Abrir |