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Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair
Open accessAbstract
Background: Advancing structural and functional maturation of stem cell–derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions. Methods: We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell–derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We used morphological, functional, and transcriptome analyses to benchmark maturation of EHM. Results: EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β 1- and β 2-adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and N-terminal pro B-type natriuretic peptide release; all are classical hallmarks of heart failure. In addition, we demonstrate the scalability of EHM according to anticipated clinical demands for cardiac repair. Conclusions: We provide proof-of-concept for a universally applicable technology for the engineering of macroscale human myocardium for disease modeling and heart repair from embryonic and induced pluripotent stem cell–derived cardiomyocytes under defined, serum-free conditions.
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Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668
Plasma Norepinephrine as a Guide to Prognosis in Patients with Chronic Congestive Heart Failure
Cohn, J. N., Levine, T. B., Olivari, M. T., Garberg, V., Lura, D., Francis, G. S., Simon, A. B., & Rector, T. (1984) · New England Journal of Medicine · doi:10.1056/nejm198409273111303 · Cited by 3,125
Chemically defined generation of human cardiomyocytes
Burridge, P. W., Matsa, E., Shukla, P., Lin, Z. C., Churko, J. M., Ebert, A. D., Lan, F., Diecke, S., Huber, B., Mordwinkin, N. M., et al. (2014) · Nature Methods · doi:10.1038/nmeth.2999 · Cited by 1,606
Self-citationHuman cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population
Yang, L., Soonpaa, M. H., Adler, E. D., Roepke, T. K., Kattman, S. J., Kennedy, M., Henckaerts, E., Bonham, K., Abbott, G. W., Linden, R. M., et al. (2008) · Nature · doi:10.1038/nature06894 · Cited by 1,389
Self-citationStructural and Functional Maturation of Cardiomyocytes Derived from Human Pluripotent Stem Cells
Lundy, S. D., Zhu, W.-Z., Regnier, M., & Laflamme, M. A. (2013) · Stem Cells and Development · doi:10.1089/scd.2012.0490 · Cited by 738
Growth of engineered human myocardium with mechanical loading and vascular coculture
Tulloch, N. L., Muskheli, V., Razumova, M. V., Korte, F. S., Regnier, M., Hauch, K. D., Pabon, L., Reinecke, H., & Murry, C. E. (2011) · Circulation Research · doi:10.1161/circresaha.110.237206 · Cited by 666
Human engineered heart tissue as a versatile tool in basic research and preclinical toxicology
Schaaf, S., Shibamiya, A., Mewe, M., Eder, A., Stöhr, A., Hirt, M. N., Rau, T., Zimmermann, W.-H., Conradi, L., Eschenhagen, T., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026397 · Cited by 365
Self-citationKamakura, T., Makiyama, T., Sasaki, K., Yoshida, Y., Wuriyanghai, Y., Chen, J., Hattori, T., Ohno, S., Kita, T., Horie, M., et al. (2013) · Circulation Journal · doi:10.1253/circj.cj-12-0987 · Cited by 295
Research works printed but not linked: 36
- 10.1126/science.282.5391.1145 · DOI · Paper page
- 10.1016/j.cell.2007.11.019 · DOI · Paper page
- 10.1016/j.stem.2011.12.013 · DOI · Paper page
- 10.1038/nbt1327 · DOI · Paper page
- 10.1002/(SICI)1097-0290(20000405)68:1<106::AID-BIT13>3.0.CO;2-3 · DOI · Paper page
- 10.1073/pnas.0407817101 · DOI · Paper page
- 10.1096/fasebj.14.5.669 · DOI · Paper page
- 10.1038/nmeth.2524 · DOI · Paper page
- 10.1016/j.biomaterials.2013.04.026 · DOI · Paper page
- 10.1002/0471143030.cb2308s55 · DOI
- 10.1161/CIRCRESAHA.115.306985 · DOI · Paper page
- 10.1126/scitranslmed.aaf8781 · DOI · Paper page
- 10.1172/JCI12131 · doi:10.1172/jci12131 · Paper page
- 10.1038/nmeth748 · DOI
- 10.1038/nbt1362 · DOI · Paper page
- 10.1089/scd.2011.0254 · DOI
- 10.1016/j.stem.2012.09.013 · DOI · Paper page
- 10.1111/j.1432-0436.2007.00236.x · DOI · Paper page
- 10.1093/bioinformatics/btp616 · DOI · Paper page
- 10.1161/CIRCRESAHA.111.251843 · DOI
- 10.1038/nbt.2005 · DOI · Paper page
- 10.1161/CIRCULATIONAHA.105.001560 · DOI · Paper page
- 10.1002/(SICI)1521-1878(200002)22:2<188::AID-BIES10>3.0.CO;2-T · doi:10.1002/(sici)1521-1878(200002)22:2<188::aid-bies10>3.0.co;2-t
- 10.4061/2011/658958 · DOI
- 10.1203/PDR.0b013e318199093c · DOI
- 10.1161/01.CIR.85.5.1743 · DOI · Paper page
- Flesch M, Kilter H, Cremers B, Lenz O, Südkamp M, Kuhn-Regnier F, Böhm M. Acute effects of nitric oxide and cyclic GMP on human myocardial contractility. J Pharmacol Exp Ther. 1997;281:1340–1349. · DOI
- 10.1111/jcmm.12356 · DOI
- 10.1373/clinchem.2006.069575 · DOI · Paper page
- 10.1177/1087057113500812 · DOI
- 10.1038/nm1394 · DOI · Paper page
- 10.1083/jcb.200204092 · doi:10.1083/jcb.200204092
- 10.1161/CIRCRESAHA.113.300216 · DOI
- 10.1161/01.CIR.102.15.1814 · DOI
- 10.1096/fj.15-280982 · DOI
- 10.1161/CIRCRESAHA.117.306143 · DOI
Cited by
A Platform for Generation of Chamber-Specific Cardiac Tissues and Disease Modeling
Zhao, Y., Rafatian, N., Feric, N. T., Cox, B. J., Aschar-Sobbi, R., Wang, E. Y., Aggarwal, P., Zhang, B., Conant, G., Ronaldson-Bouchard, K., et al. (2019) · Cell · doi:10.1016/j.cell.2018.11.042 · Cited by 610
Self-citationGiacomelli, E., Meraviglia, V., Campostrini, G., Cochrane, A., Cao, X., van Helden, R. W. J., Krotenberg Garcia, A., Mircea, M., Kostidis, S., Davis, R. P., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.05.004 · Cited by 622
Cardioids reveal self-organizing principles of human cardiogenesis
Hofbauer, P., Jahnel, S. M., Papai, N., Giesshammer, M., Deyett, A., Schmidt, C., Penc, M., Tavernini, K., Grdseloff, N., Meledeth, C., et al. (2021) · Cell · doi:10.1016/j.cell.2021.04.034 · Cited by 588
Mills, R. J., Titmarsh, D. M., Koenig, X., Parker, B. L., Ryall, J. G., Quaife-Ryan, G. A., Voges, H. K., Hodson, M. P., Ferguson, C., Drowley, L., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1707316114 · Cited by 478
Self-citationGao, L., Gregorich, Z. R., Zhu, W., Mattapally, S., Oduk, Y., Lou, X., Kannappan, R., Borovjagin, A. V., Walcott, G. P., Pollard, A. E., et al. (2018) · Circulation · doi:10.1161/circulationaha.117.030785 · Cited by 465
Metadata
- Authors
- Tiburcy, M., Hudson, J. E., Balfanz, P., Schlick, S., Meyer, T., Chang Liao, M.-L., Levent, E., Raad, F., Zeidler, S., Wingender, E., Riegler, J., Wang, M., Gold, J. D., Kehat, I., Wettwer, E., Ravens, U., Dierickx, P., van Laake, L. W., Goumans, M. J., Khadjeh, S., Toischer, K., Hasenfuss, G., Couture, L. A., Unger, A., Linke, W. A., Araki, T., Neel, B., Keller, G., Gepstein, L., Wu, J. C., & Zimmermann, W.-H.
- Venue
- Circulation
- Published
- 2017-05-09
- Volume
- 135
- Issue
- 19
- Pages
- 1832-1847
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2587079466
- Cited by
- 645
- References
- 12
- FWCI
- 23.49
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Tiburcy, M., Hudson, J. E., Balfanz, P., Schlick, S., Meyer, T., Chang Liao, M.-L., Levent, E., Raad, F., Zeidler, S., Wingender, E., Riegler, J., Wang, M., Gold, J. D., Kehat, I., Wettwer, E., Ravens, U., Dierickx, P., van Laake, L. W., Goumans, M. J., . . . Zimmermann, W.-H. (2017). Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair. Circulation. https://doi.org/10.1161/circulationaha.116.024145
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