Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype
Open accessAbstract
The 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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Fibrin hydrogel provides abundant cell attachment sites that facilitate cell spreading and function and enable macroscopic tissue compactions that yield high cell density and cellular alignment.
“Fibrin hydrogel provides abundant cell attachment sites that facilitate cell spreading and function and enable macroscopic tissue compactions that yield high cell density and cellular alignment 62 .”
From Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities (2023) · cites this paper as [62]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
Lian, X., Zhang, J., Azarin, S. M., Zhu, K., Hazeltine, L. B., Bao, X., Hsiao, C., Kamp, T. J., & Palecek, S. P. (2013) · Nature Protocols · doi:10.1038/nprot.2012.150 · Cited by 1,748 · see citing works
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 · see citing works
Advanced maturation of human cardiac tissue grown from pluripotent stem cells
Ronaldson-Bouchard, K., Ma, S. P., Yeager, K., Chen, T., Song, L., Sirabella, D., Morikawa, K., Teles, D., Yazawa, M., & Vunjak-Novakovic, G. (2018) · Nature · doi:10.1038/s41586-018-0016-3 · Cited by 1,272 · see citing works
Self-citationBiowire: a platform for maturation of human pluripotent stem cell–derived cardiomyocytes
Nunes, S. S., Miklas, J. W., Liu, J., Aschar-Sobbi, R., Xiao, Y., Zhang, B., Jiang, J., Massé, S., Gagliardi, M., Hsieh, A., et al. (2013) · Nature Methods · doi:10.1038/nmeth.2524 · Cited by 952 · see citing works
Tissue Engineering of a Differentiated Cardiac Muscle Construct
Zimmermann, W.-H., Schneiderbanger, K., Schubert, P., Didié, M., Münzel, F., Heubach, J. F., Kostin, S., Neuhuber, W. L., & Eschenhagen, T. (2002) · Circulation Research · doi:10.1161/hh0202.103644 · Cited by 917 · see citing works
Radisic, M., Park, H., Shing, H., Consi, T. R., Schöen, F. J., Langer, R., Freed, L. E., & Vunjak‐Novakovic, G. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407817101 · Cited by 913 · see citing works
Self-citationOrgans-on-a-Chip: A Fast Track for Engineered Human Tissues in Drug Development
Ronaldson-Bouchard, K., & Vunjak-Novakovic, G. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.02.011 · Cited by 657 · see citing works
Self-citationA 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 · see citing works
Self-citationElectrical stimulation systems for cardiac tissue engineering
Tandon, N. M., Cannizzaro, C., Chao, P. G., Maidhof, R., Marsano, A., Au, H. T. H., Radisic, M., & Vunjak‐Novakovic, G. (2009) · Nature Protocols · doi:10.1038/nprot.2008.183 · Cited by 531 · see citing works
Self-citationDevelopment of a drug screening platform based on engineered heart tissue
Hansen, A., Eder, A., Bönstrup, M., Flato, M., Mewe, M., Schaaf, S., Aksehirlioglu, B., Schwörer, A., Uebeler, J., & Eschenhagen, T. (2010) · Circulation Research · doi:10.1161/circresaha.109.211458 · Cited by 510 · see citing works
Measuring cell-generated forces: a guide to the available tools
Polacheck, W. J., & Chen, C. S. (2016) · Nature Methods · doi:10.1038/nmeth.3834 · Cited by 483 · see citing works
Ruan, J.-L., Tulloch, N. L., Razumova, M. V., Saiget, M., Muskheli, V., Pabon, L., Reinecke, H., Regnier, M., & Murry, C. E. (2016) · Circulation · doi:10.1161/circulationaha.114.014998 · Cited by 467 · see citing works
Sala, L., van Meer, B. J., Tertoolen, L. G. J., Bakkers, J., Bellin, M., Davis, R. P., Denning, C., Dieben, M. A. E., Eschenhagen, T., Giacomelli, E., et al. (2018) · Circulation Research · doi:10.1161/circresaha.117.312067 · Cited by 416 · see citing works
Boudou, T., Legant, W. R., Mu, A., Borochin, M. A., Thavandiran, N., Radisic, M., Zandstra, P. W., Epstein, J. A., Margulies, K. B., & Chen, C. S. (2012) · Tissue Engineering Part A · doi:10.1089/ten.tea.2011.0341 · Cited by 413 · see citing works
Parikh, S. S., Blackwell, D. J., Gómez‐Hurtado, N., Frisk, M., Wang, L., Kim, K., Dahl, C. P., Fiane, A. E., Tønnessen, T., Kryshtal, D. O., et al. (2017) · Circulation Research · doi:10.1161/circresaha.117.311920 · Cited by 370 · see citing works
Concise Review: Maturation Phases of Human Pluripotent Stem Cell-Derived Cardiomyocytes
Robertson, C., Tran, D., & George, S. C. (2013) · Stem Cells · doi:10.1002/stem.1331 · Cited by 354 · see citing works
Clinical and Mechanistic Insights Into the Genetics of Cardiomyopathy
Burke, M. A., Cook, S. A., Seidman, J. G., & Seidman, C. E. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.08.079 · Cited by 324 · see citing works
Huebsch, N., Loskill, P., Mandegar, M. A., Marks, N. C., Sheehan, A. S., Ma, Z., Mathur, A., Nguyen, T., Yoo, J. C., Judge, L. M., et al. (2014) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2014.0283 · Cited by 308 · see citing works
Differentiation of cardiomyocytes and generation of human engineered heart tissue
Breckwoldt, K., Letuffe-Brenière, D., Mannhardt, I., Schulze, T., Ulmer, B., Werner, T., Benzin, A., Klampe, B., Reinsch, M. C., Laufer, S., et al. (2017) · Nature Protocols · doi:10.1038/nprot.2017.033 · Cited by 272 · see citing works
Maturing human pluripotent stem cell-derived cardiomyocytes in human engineered cardiac tissues
Feric, N. T., & Radisic, M. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.04.019 · Cited by 247 · see citing works
Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium
Turnbull, I. C., Karakikes, I., Serrao, G. W., Backeris, P., Lee, J., Xie, C., Senyei, G., Gordon, R. E., Li, R. A., Akar, F. G., et al. (2014) · The FASEB Journal · doi:10.1096/fj.13-228007 · Cited by 184 · see citing works
Autonomous beating rate adaptation in human stem cell-derived cardiomyocytes
Eng, G. M., Lee, B. W., Protas, L., Gagliardi, M., Brown, K. R., Kass, R. S., Keller, G. M., Robinson, R. B., & Vunjak‐Novakovic, G. (2016) · Nature Communications · doi:10.1038/ncomms10312 · Cited by 178 · see citing works
Self-citationThyroid hormone drives fetal cardiomyocyte maturation
Chattergoon, N. N., Giraud, G. D., Louey, S., Stork, P. A., Fowden, A. L., & Thornburg, K. L. R. (2011) · The FASEB Journal · doi:10.1096/fj.10-179895 · Cited by 170 · see citing works
Physiologic force-frequency response in engineered heart muscle by electromechanical stimulation
Godier-Furnémont, A., Tiburcy, M., Wagner, E., Dewenter, M., Lämmle, S., El‐Armouche, A., Lehnart, S. E., Vunjak‐Novakovic, G., & Zimmermann, W. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.03.055 · Cited by 157 · see citing works
Self-citationMordwinkin, N. M., Burridge, P. W., & Wu, J. C. (2012) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-012-9423-2 · Cited by 128 · see citing works
Piccini, J. P., Whellan, D. J., Berridge, B. R., Finkle, J. K., Pettit, S. D., Stockbridge, N., Valentin, J., Vargas, H. M., & Krucoff, M. W. (2009) · American Heart Journal · doi:10.1016/j.ahj.2009.06.007 · Cited by 125 · see citing works
Petriccione, M., Mastrobuoni, F., Zampella, L., & Scortichini, M. (2015) · Scientific Reports · doi:10.1038/srep16961 · Cited by 117 · see citing works
Automated drug screening with contractile muscle tissue engineered from dystrophic myoblasts
Vandenburgh, H. H., Shansky, J., Benesch, F., Skelly, K., Spinazzola, J. M., Saponjian, Y., & Tseng, B. S. (2009) · The FASEB Journal · doi:10.1096/fj.09-134411 · Cited by 110 · see citing works
Encapsulation of Cardiomyocytes in a Fibrin Hydrogel for Cardiac Tissue Engineering
Ye, K. Y., Sullivan, K. E., & Black, L. D. (2011) · Journal of Visualized Experiments · doi:10.3791/3251 · Cited by 77 · see citing works
Hayakawa, T., Kunihiro, T., Dowaki, S., Uno, H., Matsui, E., Uchida, M., Kobayashi, S., Yasuda, A., Shimizu, T., & Okano, T. (2011) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2011.0273 · Cited by 68 · see citing works
The developmental transcriptome of the human heart
Pervolaraki, E., Dachtler, J., Anderson, R. A., & Holden, A. V. (2018) · Scientific Reports · doi:10.1038/s41598-018-33837-6 · Cited by 44 · see citing works
Generation of Strip-Format Fibrin-Based Engineered Heart Tissue (EHT)
Schaaf, S., Eder, A., Vollert, I., Stoehr, A., Hansen, A., & Eschenhagen, T. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-1047-2_11 · Cited by 41 · see citing works
Sala, L., van Meer, B. J., Tertoolen, L. G. J., Bakkers, J., Bellin, M., Davis, R. P., Denning, C. N., Dieben, M. A. E., Thomas Eschenhagen, A., Giacomelli, E., et al. (2018) · Utrecht University Repository (Utrecht University) · Cited by 22 · see citing works
White, M. C., Pang, L., & Yang, X. (2016) · Food and Chemical Toxicology · doi:10.1016/j.fct.2016.05.025 · Cited by 17 · see citing works
Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes
Zimmermann, W. H., Fink, C., Kralisch, D., Remmers, U., Weil, J., & Eschenhagen, T. (2000) · Biotechnology and Bioengineering · doi:10.1002/(sici)1097-0290(20000405)68:1
Flagged first, then by citations
Research works printed but not linked: 3
- [20]Robertson C, Tran DD, and George SC, Concise Review: Maturation Phases of Human Pluripotent Stem Cell-Derived Cardiomyocytes. STEM CELLS, 2013 31(5): p. 829– 837. 23355363 PMC3749929
- Radisic M, PNAS 101(52), 18129– 18134 (2004). DOI: 10.1073/pnas.0407817101 15604141 PMC539727 · DOI
- Ronaldson - Bouchard K, Nature, 556(7700), 239– 243 (2018) DOI: 10.1038/s41586-018-0016-3 29618819 PMC5895513 · DOI · Paper page
Cited by
Sorted by citations
A multi-organ chip with matured tissue niches linked by vascular flow
Ronaldson-Bouchard, K., Teles, D., Yeager, K., Tavakol, D. N., Zhao, Y., Chramiec, A., Tagore, S., Summers, M., Stylianos, S., Tamargo, M., et al. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00882-6 · Cited by 512 · see citing works
Self-citationInduced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications
Cerneckis, J., Cai, H., & Shi, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01809-0 · Cited by 452 · see citing works
Human disease models in drug development
Loewa, A., Feng, J. J., & Hedtrich, S. (2023) · Nature Reviews Bioengineering · doi:10.1038/s44222-023-00063-3 · Cited by 331 · see citing works
Multi-lineage human iPSC-derived platforms for disease modeling and drug discovery
Sharma, A., Sances, S., Workman, M. J., & Svendsen, C. N. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.02.011 · Cited by 296 · see citing works
Organs-on-a-chip models for biological research
Vunjak-Novakovic, G., Ronaldson-Bouchard, K., & Radisic, M. (2021) · Cell · doi:10.1016/j.cell.2021.08.005 · Cited by 248 · see citing works
“An example is the engineered heart muscle matured by electromechanical conditioning with the force generation and conduction developing more slowly and to a lesser extent than structural features (Ronaldson-Bouchard et al., 2018; Ronaldson-Bouchard et al., 2019).”
BackgroundSelf-citationComplex Relationship Between Cardiac Fibroblasts and Cardiomyocytes in Health and Disease
Hall, C., Gehmlich, K., Denning, C. N., & Pavlović, D. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.019338 · Cited by 207 · see citing works
Next generation of heart regenerative therapies: progress and promise of cardiac tissue engineering
Tenreiro, M. F., Louro, A. F., Alves, P. M., & Serra, M. (2021) · npj Regenerative Medicine · doi:10.1038/s41536-021-00140-4 · Cited by 145 · see citing works
Lyra‐Leite, D. M., Gutiérrez‐Gutiérrez, Ó., Wang, M., Zhou, Y., Cyganek, L., & Burridge, P. W. (2022) · STAR Protocols · doi:10.1016/j.xpro.2022.101560 · Cited by 136 · see citing works
Bliley, J. M., Vermeer, M. C. S. C., Duffy, R. M., Batalov, I., Kramer, D., Tashman, J. W., Shiwarski, D. J., Lee, A. R., Teplenin, A. S., Volkers, L., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abd1817 · Cited by 134 · see citing works
Chramiec, A. G., Teles, D., Yeager, K. J., Marturano-Kruik, A., Pak, J., Chen, T. F., Hao, L. Y., Wang, M. C., Lock, R. I., Tavakol, D. N., et al. (2020) · Lab on a Chip · doi:10.1039/d0lc00424c · Cited by 119 · see citing works
Self-citationZhuang, R. Z., Lock, R., Liu, B., & Vunjak-Novakovic, G. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00885-3 · Cited by 84 · see citing works
Self-citationWhen Stiffness Matters: Mechanosensing in Heart Development and Disease
Gaetani, R., Zizzi, E. A., Deriu, M. A., Morbiducci, U., Pesce, M., & Messina, E. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00334 · Cited by 81 · see citing works
Criscione, J. D., Rezaei, Z., Cantu, C. M. H., Murphy, S. A., Shin, S. R., & Kim, D. (2022) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2022.114840 · Cited by 78 · see citing works
Microengineered platforms for characterizing the contractile function of in vitro cardiac models
Dou, W., Malhi, M., Zhao, Q., Wang, L., Huang, Z., Law, J., Liu, N., Simmons, C. A., Maynes, J. T., & Sun, Y. (2022) · Microsystems & Nanoengineering · doi:10.1038/s41378-021-00344-0 · Cited by 80 · see citing works
Advances in development and application of human organoids
Shankaran, A., Prasad, K., Chaudhari, S., Brand, A. M., & Satyamoorthy, K. (2021) · 3 Biotech · doi:10.1007/s13205-021-02815-7 · Cited by 74 · see citing works
Reconstructing the heart using iPSCs: Engineering strategies and applications
Cho, S., Lee, C., Skylar‐Scott, M. A., Heilshorn, S. C., & Wu, J. C. (2021) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2021.04.006 · Cited by 71 · see citing works
Fenix, A. M., Miyaoka, Y., Bertero, A., Blue, S. M., Spindler, M. J., Tan, K. K. B., Pérez-Bermejo, J. A., Chan, A. H., Mayerl, S. J., Nguyen, T., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26623-y · Cited by 67 · see citing works
Vuckovic, S., Dinani, R., Nollet, E. E., Kuster, D. W. D., Buikema, J. W., Houtkooper, R. H., Nabben, M., van der Velden, J., & Goversen, B. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-03021-9 · Cited by 75 · see citing works
Lovecchio, J., Gargiulo, P., Luna, J. L. V., Giordano, E., & Sigurjónsson, Ó. E. (2019) · Scientific Reports · doi:10.1038/s41598-019-53319-7 · Cited by 63 · see citing works
Dwyer, K. D., & Coulombe, K. L. K. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.12.015 · Cited by 61 · see citing works
Latest Advances in 3D Bioprinting of Cardiac Tissues
Jafari, A., Ajji, Z., Mousavi, A., Naghieh, S., Bencherif, S. A., & Savoji, H. (2022) · Advanced Materials Technologies · doi:10.1002/admt.202101636 · Cited by 59 · see citing works
Liang, J., Wu, M., Chen, C., Mai, M., Huang, J., & Zhu, P. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/2102841 · Cited by 56 · see citing works
Engineered models of the human heart: Directions and challenges
Stein, J. M., Mummery, C. L., & Bellin, M. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2020.11.013 · Cited by 54 · see citing works
Pourrier, M., & Fedida, D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020657 · Cited by 52 · see citing works
Song, Y., Uchida, H., Sharipol, A., Piraino, L. R., Mereness, J. A., Ingalls, M. H., Rebhahn, J. A., Newlands, S. D., DeLouise, L. A., Ovitt, C. E., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-01876-x · Cited by 51 · see citing works
Iuliano, A., van der Wal, E., Ruijmbeek, C. W. B., Groen, S. L. M. I. ‘., Pijnappel, W. W. M. P., de Greef, J. C., & Saggiomo, V. (2020) · Advanced Materials Technologies · doi:10.1002/admt.202000344 · Cited by 49 · see citing works
Novelli, G., Spitalieri, P., Murdocca, M., Centanini, E., & Sangiuolo, F. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1059579 · Cited by 43 · see citing works
Tamargo, M. A., Nash, T. R., Fleischer, S., Kim, Y., Vila, O. F., Yeager, K. J., Summers, M., Zhao, Y., Lock, R. I., Chavez, M., et al. (2021) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.1c01006 · Cited by 43 · see citing works
Self-citationMao, M., Qu, X., Zhang, Y., Gu, B., Li, C., Liu, R., Li, X., Zhu, H., He, J., & Li, D. (2023) · Nature Communications · doi:10.1038/s41467-023-37716-1 · Cited by 42 · see citing works
Massai, D., Pisani, G., Isu, G., Rodríguez, A., Cerino, G., Galluzzi, R., Pisanu, A., Tonoli, A., Bignardi, C., Audenino, A. L., et al. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00733 · Cited by 43 · see citing works
Xu, F., Jin, H., Liu, L., Yang, Y., Cen, J., Wu, Y., Chen, S., & Sun, D. (2024) · Microsystems & Nanoengineering · doi:10.1038/s41378-024-00692-7 · Cited by 41 · see citing works
Proliferation and Maturation: Janus and the Art of Cardiac Tissue Engineering
Singh, B. N., Yücel, D., Garay, B. I., Tolkacheva, E. G., Kyba, M., Perlingeiro, R. C. R., van Berlo, J. H., & Ogle, B. M. (2023) · Circulation Research · doi:10.1161/circresaha.122.321770 · Cited by 39 · see citing works
Han, K., Mao, M., Fu, L., Zhang, Y., Kang, Y., Li, D., & He, J. (2024) · Small · doi:10.1002/smll.202401561 · Cited by 34 · see citing works
Regenerative Medicine Clinical Readiness
Yamada, S., Behfar, A., & Terzic, A. (2021) · Regenerative Medicine · doi:10.2217/rme-2020-0178 · Cited by 34 · see citing works
FRESH™ 3D bioprinted cardiac tissue, a bioengineered platform for in vitro pharmacology
Finkel, S., Sweet, S., Locke, T., Smith, S., Wang, Z., Sandini, C., Imredy, J. P., He, Y., Durante, M. R., Lagrutta, A., et al. (2023) · APL Bioengineering · doi:10.1063/5.0163363 · Cited by 33 · see citing works
Advances in 3D Bioprinted Cardiac Tissue Using Stem Cell-Derived Cardiomyocytes
Bliley, J. M., Stang, M. A., Behre, A., & Feinberg, A. W. (2024) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szae014 · Cited by 38 · see citing works
Heart regeneration using pluripotent stem cells
Kadota, S., Tanaka, Y., & Shiba, Y. (2020) · Journal of Cardiology · doi:10.1016/j.jjcc.2020.03.013 · Cited by 33 · see citing works
Tracy, E. P., Gettler, B. C., Zakhari, J. S., Schwartz, R. J., Williams, S. K., & Birla, R. K. (2020) · Cardiovascular Engineering and Technology · doi:10.1007/s13239-020-00478-8 · Cited by 32 · see citing works
Machine Learning Techniques to Classify Healthy and Diseased Cardiomyocytes by Contractility Profile
Teles, D., Kim, Y., Ronaldson-Bouchard, K., & Vunjak‐Novakovic, G. (2021) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.1c00418 · Cited by 32 · see citing works
Self-citationSerna, J. A., Rueda-Gensini, L., Céspedes-Valenzuela, D. N., Cifuentes, J., Cruz, J. C., & Muñoz-Camargo, C. (2021) · Polymers · doi:10.3390/polym13193263 · Cited by 33 · see citing works
Engineered Maturation Approaches of Human Pluripotent Stem Cell-Derived Ventricular Cardiomyocytes
Ge, F., Wang, Z., & Xi, J. (2019) · Cells · doi:10.3390/cells9010009 · Cited by 29 · see citing works
Sleiman, Y., Lacampagne, A., & Méli, A. C. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04337-9 · Cited by 27 · see citing works
Mending a broken heart: In vitro, in vivo and in silico models of congenital heart disease
Rufaihah, A. J., Chen, C.-K., Yap, C., & Mattar, C. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.047522 · Cited by 25 · see citing works
Jiménez‐Vázquez, E. N., Arad, M., Macías, Á., Vera-Pedrosa, M. L., Cruz, F. M., Gutiérrez, L. K., Cuttitta, A. J., da Rocha, A. M., Herron, T. J., Ponce‐Balbuena, D., et al. (2022) · eLife · doi:10.7554/elife.76576 · Cited by 28 · see citing works
Mini-review: advances in 3D bioprinting of vascularized constructs
Bova, L., Billi, F., & Cimetta, E. (2020) · Biology Direct · doi:10.1186/s13062-020-00273-4 · Cited by 27 · see citing works
Salem, T. T., Frankman, Z. D., & Churko, J. M. (2021) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2021.0088 · Cited by 27 · see citing works
Mao, M., Han, K., Gao, J., Ren, Z., Zhang, Y., He, J., & Li, D. (2025) · Advanced Materials · doi:10.1002/adma.202419380 · Cited by 23 · see citing works
Multicellular 3D Models for the Study of Cardiac Fibrosis
Picchio, V., Floris, E., Derevyanchuk, Y., Cozzolino, C., Messina, E., Pagano, F., Chimenti, I., & Gaetani, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911642 · Cited by 22 · see citing works
Nanoenabled Trainable Systems: From Biointerfaces to Biomimetics
Li, P., Kim, S., & Tian, B. (2022) · ACS Nano · doi:10.1021/acsnano.2c08042 · Cited by 23 · see citing works
Mikhailov, A., Kalyanasundaram, A., Li, N., Scott, S. S., Artiga, E. J., Subr, M., Zhao, J., Hansen, B. J., Hummel, J. D., & Fedorov, V. V. (2020) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2020.10.012 · Cited by 22 · see citing works
Recent progress in induced pluripotent stem cell-derived 3D cultures for cardiac regeneration
Wang, K., Xue, Q., Xu, X.-H., Hu, F., & Shao, H. J. (2021) · Cell and Tissue Research · doi:10.1007/s00441-021-03414-x · Cited by 21 · see citing works
Membrane Remodeling of Human-Engineered Cardiac Tissue by Chronic Electric Stimulation
Rubfiaro, A. S., Prajapati, N. J., Paolino, L., Lou, L., Cotayo, D., Pandey, P., Shaver, M., Hutcheson, J. D., Agarwal, A. K., & He, J. M. (2023) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.2c01370 · Cited by 21 · see citing works
English, E. J., Samolyk, B. L., Gaudette, G. R., & Pins, G. D. (2023) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37530 · Cited by 21 · see citing works
Gu, B., Han, K., Cao, H., Huang, X., Li, X., Mao, M., Zhu, H., Cai, H., Li, D., & He, J. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100914 · Cited by 23 · see citing works
Cardiac Tissue Engineering: Inclusion of Non-cardiomyocytes for Enhanced Features
Munawar, S., & Turnbull, I. C. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.653127 · Cited by 20 · see citing works
Gabetti, S., Sileo, A., Montrone, F., Putame, G., Audenino, A. L., Marsano, A., & Massai, D. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1031183 · Cited by 20 · see citing works
Building Valveless Impedance Pumps From Biological Components: Progress and Challenges
Sarvazyan, N. A. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2021.770906 · Cited by 19 · see citing works
Complex architectural control of ice-templated collagen scaffolds using a predictive model
Cyr, J. A., Husmann, A., Best, S. M., & Cameron, R. E. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.09.034 · Cited by 19 · see citing works
Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects
Dame, K., & Ribeiro, A. J. S. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370220959598 · Cited by 19 · see citing works
Sphabmixay, P., Raredon, M. S. B., Wang, A. J.-S., Lee, H., Hammond, P. T., Fang, N. X., & Griffith, L. G. (2021) · Biofabrication · doi:10.1088/1758-5090/ac23aa · Cited by 20 · see citing works
Building blocks of microphysiological system to model physiology and pathophysiology of human heart
Vuorenpää, H., Björninen, M., Välimäki, H., Ahola, A., Kroon, M., Honkamäki, L., Koivumäki, J. T., & Pekkanen-Mattila, M. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1213959 · Cited by 19 · see citing works
Pioner, J. M., Fornaro, A., Coppini, R., Ceschia, N., Sacconi, L., Donati, M. A., Favilli, S., Poggesi, C., Olivotto, I., & Ferrantini, C. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00368 · Cited by 18 · see citing works
Cyr, J. A., Colzani, M., Bayraktar, S., Köhne, M., Bax, D. V., Graup, V., Farndale, R. W., Sinha, S., Best, S. M., & Cameron, R. E. (2023) · Biomaterials Advances · doi:10.1016/j.bioadv.2023.213680 · Cited by 17 · see citing works
Wong, A. O.-T., Wong, N., Geng, L., Chow, M. Z.-Y., Lee, E. K., Wu, H., Khine, M., Kong, C., Costa, K. D., Keung, W., et al. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00165 · Cited by 15 · see citing works
Whole Heart Engineering: Advances and Challenges
Morrissey, J., Mesquita, F., Hochman‐Mendez, C., & Taylor, D. A. (2021) · Cells Tissues Organs · doi:10.1159/000511382 · Cited by 15 · see citing works
Lou, L., Rubfiaro, A. S., He, J. M., & Agarwal, A. K. (2023) · Nanoscale · doi:10.1039/d3nr01553j · Cited by 14 · see citing works
Elkhoury, K., Kodeih, S., Enciso‐Martínez, E., Maziz, A., & Bergaud, C. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202303288 · Cited by 14 · see citing works
Multifocus microscopy with optical sectioning and high axial resolution
Ströhl, F., Hansen, D. H., Grifo, M. N., & Birgisdottir, Å. B. (2022) · Optica · doi:10.1364/optica.468583 · Cited by 13 · see citing works
Marino, S., Al-Hijailan, R. S., Alonaizan, R., Gabetti, S., Massai, D., & Pesce, M. (2025) · Gels · doi:10.3390/gels11080593 · Cited by 12 · see citing works
The Current State of Realistic Heart Models for Disease Modelling and Cardiotoxicity
Kistamás, K., Lamberto, F., Vaičiulevičiūtė, R., Leal, F., Muenthaisong, S., Marte, L., Subías-Beltrán, P., Alaburda, A., Arvanitis, D. N., Zana, M., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179186 · Cited by 13 · see citing works
Souidi, M., Sleiman, Y., Aćimović, I., Přibyl, J., Charrabi, A., Baecker, V., Scheuermann, V., Pešl, M., Jelínková, Š., Skládal, P., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020662 · Cited by 12 · see citing works
Lou, L., Rubfiaro, A. S., He, J. M., & Agarwal, A. K. (2021) · Advanced Materials Technologies · doi:10.1002/admt.202100669 · Cited by 12 · see citing works
Engineering Cardiovascular Tissue Chips for Disease Modeling and Drug Screening Applications
Chan, A., & Huang, N. F. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.673212 · Cited by 10 · see citing works
Novel, low-cost bioreactor for in vitro electrical stimulation of cardiac cells
Licata, J. P., Gerstenhaber, J. A., & Lelkes, P. I. (2025) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2025.1531731 · Cited by 11 · see citing works
Kobeissi, H., Jilberto, J., Karakan, M. Ç., Gao, X., DePalma, S. J., Das, S. L., Quach, L., Urquia, J., Baker, B. M., Chen, C. S., et al. (2024) · PLoS ONE · doi:10.1371/journal.pone.0298863 · Cited by 11 · see citing works
Integrating Hierarchical Vasculature into Engineered Cardiac Tissues
Zhuang, R. Z., Chesnais, F., & Vunjak‐Novakovic, G. (2025) · Advanced Materials · doi:10.1002/adma.202509242 · Cited by 10 · see citing works
Self-citationLy, O. T., Brown, G. E., Han, Y. D., Darbar, D., & Khetani, S. R. (2021) · Experimental Biology and Medicine · doi:10.1177/15353702211009146 · Cited by 12 · see citing works
The HH-GLI2-CKS1B network regulates the proliferation-to-maturation transition of cardiomyocytes
Waldron, C. J., Kelly, L. A., Stan, N., Kawakami, Y., Abrahante, J. E., Magli, A., Ogle, B. M., & Singh, B. N. (2024) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szae032 · Cited by 9 · see citing works
Knierim, M., Bommer, T., Paulus, M. G., Riedl, D., Fink, S., Pöppl, A., Reetz, F., Wang, P., Maier, L. S., Voigt, N., et al. (2024) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00536.2024 · Cited by 9 · see citing works
Pisanu, A., Reid, G., Fusco, D., Sileo, A., Diaz, D. R., Tarhini, H., Putame, G., Massai, D., Isu, G., & Marsano, A. (2022) · iScience · doi:10.1016/j.isci.2022.104297 · Cited by 9 · see citing works
Engineering Models of the Heart Left Ventricle
Okhovatian, S., Mohammadi, M. H., Rafatian, N., & Radisic, M. (2022) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.1c00636 · Cited by 9 · see citing works
The origin, progress, and application of cell‐based cardiac regeneration therapy
Zhuo, D., Lei, I., Li, W., Liu, L., Li, L., Ni, J., Liu, Z., & Fan, G. (2023) · Journal of Cellular Physiology · doi:10.1002/jcp.31060 · Cited by 8 · see citing works
Yadav, V., Chong, N., Ellis, B. W., Ren, X., Senapati, S., Chang, H., & Zorlutuna, P. (2020) · Lab on a Chip · doi:10.1039/d0lc00809e · Cited by 10 · see citing works
Zhang, H., Sen, P., Hamers, J., Sittig, T., Woestenburg, B., Moretti, A., Dendorfer, A., & Merkus, D. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-03741-0 · Cited by 8 · see citing works
Gao, Y., Su, L., Wei, Y., Tan, S. H., Hu, Z., Tao, Z., Kovalik, J., Soong, T. W., Zhang, J. J., Pu, J., et al. (2023) · Theranostics · doi:10.7150/thno.80801 · Cited by 8 · see citing works
Tissue engineering solutions to replace contractile function during pediatric heart surgery
Williams, S. K., & Birla, R. K. (2020) · Tissue and Cell · doi:10.1016/j.tice.2020.101452 · Cited by 8 · see citing works
Strategic use of organoids and organs-on-chip as biomimetic tools
Santos, A. K., Scalzo, S., Souza, R. T. V., Santana, P. H. G., Marques, B. L., de Oliveira, L. F., Filho, D. M., Kihara, A. H., Santiago, H. C., Parreira, R. C., et al. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.09.010 · Cited by 8 · see citing works
Modeling heart rhythm using human engineered heart tissues
Tu, C., Caudal, A., Liu, Y., Narayan, S. M., & Wu, J. C. (2025) · Nature Protocols · doi:10.1038/s41596-025-01217-w · Cited by 8 · see citing works
Building multiple microenvironmental niches using a customizable 3D printed well insert
Milton, L. A., Kasetsirikul, S., Catano, J. A. A., Hilmi, F. S., Zhou, Z., Molley, T. G., Kilian, K. A., Ong, L. J. Y., Chirnside, J., Byrom, N., et al. (2025) · Lab on a Chip · doi:10.1039/d5lc00753d · Cited by 7 · see citing works
Kumar, A., He, S., & Mali, P. (2023) · APL Bioengineering · doi:10.1063/5.0137458 · Cited by 7 · see citing works
Qu, K.-Y., Cheng, H., Qiao, L., Jiao, J., Chang, S., Peng, X., Cui, C., Zhang, F., & Huang, N. (2025) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2025.117478 · Cited by 7 · see citing works
Using hiPSC‐CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia
Arslanova, A., Shafaattalab, S., Ye, K., Asghari, P., Lin, L. Y., Kim, B., Roston, T. M., Hove‐Madsen, L., Petegem, F. V., Sanatani, S., et al. (2021) · Current Protocols · doi:10.1002/cpz1.320 · Cited by 7 · see citing works
Engineering of tissue in microphysiological systems demonstrated by modelling skeletal muscle
Gao, Y., Zhang, Z., Yao, Y., Zhang, J., Li, X., Yang, K., Si, N., Chen, Z., Gu, Z., & Yin, N. (2025) · Regenerative Biomaterials · doi:10.1093/rb/rbaf059 · Cited by 6 · see citing works
Enhanced drug classification using machine learning with multiplexed cardiac contractility assays
Aghavali, R., Roberts, E. G., Kurokawa, Y. K., Mak, E., Chan, M. Y. C., Wong, A. O. T., Li, R. A., & Costa, K. D. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107459 · Cited by 5 · see citing works
Cai, L., Zhao, Y., Li, Z., Xiao, L., Wu, Y., Wang, S., Liu, Q., Ye, Y., Guo, Y., & Zhang, D. (2025) · Advanced Science · doi:10.1002/advs.202503173 · Cited by 5 · see citing works
Gaetani, R., Derevyanchuk, Y., Notargiacomo, A., Pea, M., Renzi, M., Messina, E., & Palma, F. (2022) · Bioengineering · doi:10.3390/bioengineering9110621 · Cited by 5 · see citing works
Waldrop, T. I., Graham, C., Gard, W. A., Ingle, K. A., Ptacek, T., Nguyen, T., Lose, B., Sethu, P., & Lee, T. C. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1101622 · Cited by 5 · see citing works
Licata, J. P., Gerstenhaber, J. A., & Lelkes, P. I. (2025) · Stem Cells and Development · doi:10.1089/scd.2025.0062 · Cited by 5 · see citing works
Kołodziejek, D., Aleksandra, S., Zuzanna, I.-S., Drozd, M., Wojasiński, M., & Jastrzębska, E. (2025) · Lab on a Chip · doi:10.1039/d5lc00460h · Cited by 4 · see citing works
Mousavi, A., Boghdady, C.-M., Cui, S., Rostami, S., Shakeri, A., Rafatian, N., Aurousseau, M. R. P., Andelfinger, G., Radisic, M., Moraes, C., et al. (2025) · Small · doi:10.1002/smll.202504493 · Cited by 4 · see citing works
- Authors
- Ronaldson-Bouchard, K., Yeager, K., Teles, D., Chen, T., Ma, S., Song, L., Morikawa, K., Wobma, H. M., Vasciaveo, A., Ruiz, E. C., Yazawa, M., & Vunjak-Novakovic, G.
- Affiliations
- Columbia University (US)
- ORCID
- Venue
- Nature Protocols
- Published
- 2019-09-06
- Volume
- 14
- Issue
- 10
- Pages
- 2781-2817
- ISSN
- 1750-2799 (ISSN-L)
- 1754-2189
- PMC
- PMC7195192
- OpenAlex
- W2971619350
- Cited by
- 144
- References
- 35
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 16 · 2023: 25 · 2022: 22 · 2021: 28 · 2020: 20 · 2019: 3
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Protocols (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (2r01hl076485-16)
- National Heart, Lung, and Blood Institute (R01HL138486, R01-HL076485)
- National Institute of Biomedical Imaging and Bioengineering (UG3EB025765, UH2EB017103, UH3EB017103, UH3EB025765)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- human induced pluripotent stem cells, cardiomyocyte maturation, engineered heart tissue, electromechanical stimulation, fibrin gel, dermal fibroblasts, bioreactors, cardiac contractility, calcium handling, beta-adrenergic responsiveness, sarcomere length, T-tubules, mitochondrial density, cardiac disease modeling, drug testing
- MeSH terms
- Cell Differentiation, Heart, Humans, Myocardium, Cell Culture Techniques, Tissue Engineering, Myocytes, Cardiac, Induced Pluripotent Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
