Generation of Quiescent Cardiac Fibroblasts From Human Induced Pluripotent Stem Cells for In Vitro Modeling of Cardiac Fibrosis
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Rationale: Activated fibroblasts are the major cell type that secretes excessive extracellular matrix in response to injury, contributing to pathological fibrosis and leading to organ failure. Effective anti-fibrotic therapeutic solutions, however, are not available due to the poorly defined characteristics and unavailability of tissue-specific fibroblasts. Recent advances in single-cell RNA-sequencing fill such gaps of knowledge by enabling delineation of the developmental trajectories and identification of regulatory pathways of tissue-specific fibroblasts among different organs. Objective: This study aims to define the transcriptome profiles of tissue-specific fibroblasts using recently reported mouse single-cell RNA-sequencing atlas and to develop a robust chemically defined protocol to derive cardiac fibroblasts (CFs) from human induced pluripotent stem cells for in vitro modeling of cardiac fibrosis and drug screening. Methods and Results: By analyzing the single-cell transcriptome profiles of fibroblasts from 10 selected mouse tissues, we identified distinct tissue-specific signature genes, including transcription factors that define the identities of fibroblasts in the heart, lungs, trachea, and bladder. We also determined that CFs in large are of the epicardial lineage. We thus developed a robust chemically defined protocol that generates CFs from human induced pluripotent stem cells. Functional studies confirmed that iPSC-derived CFs preserved a quiescent phenotype and highly resembled primary CFs at the transcriptional, cellular, and functional levels. We demonstrated that this cell-based platform is sensitive to both pro- and anti-fibrosis drugs. Finally, we showed that crosstalk between human induced pluripotent stem cell-derived cardiomyocytes and CFs via the atrial/brain natriuretic peptide-natriuretic peptide receptor-1 pathway is implicated in suppressing fibrogenesis. Conclusions: This study uncovers unique gene signatures that define tissue-specific identities of fibroblasts. The bona fide quiescent CFs derived from human induced pluripotent stem cells can serve as a faithful in vitro platform to better understand the underlying mechanisms of cardiac fibrosis and to screen anti-fibrotic drugs.
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Multi-cell-type in vitro models such as spheroids, organoids, and engineered heart tissue are proficient in generating force and exhibit predictable responses to pharmacological agents.
“These models are proficient in generating force and exhibit predictable responses to pharmacological agents.[ 23 , 24 ]”
From Engineered in vitro multi-cell type ventricle model generates long-term pulsatile flow and modulates cardiac output in response to cardioactive drugs (2025) · cites this paper as [23]
The Discussion (page unavailable) reports that a cardiomyocyte–fibroblast co-culture showed an enhanced anti-fibrotic response when treated with sacubitril. It does not establish that spheroids, organoids, or engineered heart tissue generate force or show predictable pharmacological responses as a class. (LLM, conf=0.81)
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Cites
Myofibroblasts and mechano-regulation of connective tissue remodelling
Tomasek, J. J., Gabbiani, G., Hinz, B., Chaponnier, C., & Brown, R. A. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm809 · Cited by 4,290 · see citing works
Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes
Whyte, W. A., Orlando, D. A., Hnisz, D., Abraham, B. J., Lin, C. Y., Kagey, M. H., Rahl, P. B., Lee, T. I., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.03.035 · Cited by 4,143 · see citing works
Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris
The Tabula Muris Consortium, coordination, O., coordination, L., processing, O. C. A., sequencing, L. P. A., analysis, C. D., annotation, C. T., Writing group, Supplemental text writing group, & Principal investigators (2018) · Nature · doi:10.1038/s41586-018-0590-4 · Cited by 3,326 · see citing works
Pericytes: Developmental, Physiological, and Pathological Perspectives, Problems, and Promises
Armulik, A., Genové, G., & Betsholtz, C. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.07.001 · Cited by 2,653 · see citing works
Induced pluripotent stem cell technology: a decade of progress.
Shi, Y., Inoue, H., Wu, J. C., & Yamanaka, S. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.245 · Cited by 1,525 · see citing works
Self-citationRequirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis.Preprint
Molkentin, J. D., Lin, Q., Duncan, S. A., & Olson, E. N. (1997) · Genes & Development · doi:10.1101/gad.11.8.1061 · Cited by 1,152 · see citing works
Pirfenidone in idiopathic pulmonary fibrosis
Taniguchi, H., Ebina, M., Kondoh, Y., Ogura, T., Azuma, A., Suga, M., Taguchi, Y., Takahashi, H., Nakata, K., Sato, A., et al. (2009) · European Respiratory Journal · doi:10.1183/09031936.00005209 · Cited by 957 · see citing works
Forcing cells to change lineages
Graf, T., & Enver, T. (2009) · Nature · doi:10.1038/nature08533 · Cited by 899 · see citing works
Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease
Fan, D., Takawale, A., Lee, J., & Kassiri, Z. (2012) · Fibrogenesis & Tissue Repair · doi:10.1186/1755-1536-5-15 · Cited by 814 · see citing works
Pirfenidone in idiopathic pulmonary fibrosis: Figure 1–
Swigris, J., & Fairclough, D. (2010) · European Respiratory Journal · doi:10.1183/09031936.00071710 · Cited by 802 · see citing works
Karlmark, K. R., Weiskirchen, R., Zimmermann, H. W., Gassler, N., Ginhoux, F., Weber, C., Merad, M., Luedde, T., Trautwein, C., & Tacke, F. (2009) · Hepatology · doi:10.1002/hep.22950 · Cited by 782 · see citing works
IL-11 is a crucial determinant of cardiovascular fibrosis
Schafer, S., Viswanathan, S., Widjaja, A. A., Lim, W.-W., Moreno-Moral, A., DeLaughter, D. M., Ng, B., Patone, G., Chow, K., Khin, E., et al. (2017) · Nature · doi:10.1038/nature24676 · Cited by 639 · see citing works
Myocardin and ternary complex factors compete for SRF to control smooth muscle gene expression
Wang, Z., Wang, D.-Z., Hockemeyer, D. F., McAnally, J., Nordheim, A., & Olson, E. N. (2004) · Nature · doi:10.1038/nature02382 · Cited by 562 · see citing works
Organ and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications
Weiskirchen, R., Weiskirchen, S., & Tacke, F. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.06.003 · Cited by 546 · see citing works
Acharya, A., Baek, S. T., Huang, G., Eskiocak, B., Goetsch, S., Sung, C. Y., Banfi, S., Sauer, M. F., Olsen, G. S., Duffield, J. S., et al. (2012) · Development · doi:10.1242/dev.079970 · Cited by 498 · see citing works
Zeisberg, M., & Kalluri, R. (2012) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00328.2012 · Cited by 463 · see citing works
Direct lineage reprogramming: strategies, mechanisms, and applications.
Xu, J., Du, Y.-Y., & Deng, H. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.01.013 · Cited by 409 · see citing works
TIMP-2 Is Required for Efficient Activation of proMMP-2 in Vivo
Wang, Z., Jüttermann, R., & Soloway, P. D. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001270200 · Cited by 388 · see citing works
Kruppel-like Factor 4 Abrogates Myocardin-induced Activation of Smooth Muscle Gene Expression
Liu, Y., Sinha, S., McDonald, O. G., Shang, Y., Hoofnagle, M. H., & Owens, G. K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m412862200 · Cited by 362 · see citing works
Natriuretic peptide metabolism, clearance and degradation
Potter, L. R. (2011) · FEBS Journal · doi:10.1111/j.1742-4658.2011.08082.x · Cited by 359 · see citing works
GATA4 is essential for formation of the proepicardium and regulates cardiogenesis
Watt, A. J., Battle, M. A., Li, J., & Duncan, S. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400752101 · Cited by 354 · see citing works
Zile, M. R., O’Meara, E., Claggett, B. L., PRESCOTT, M. F., Solomon, S. D., Swedberg, K. B., Packer, M., McMurray, J. J. V., Shi, V. C., Lefkowitz, M. P., et al. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.11.042 · Cited by 253 · see citing works
Swaney, J. S., Roth, D. M., Olson, E. R., Naugle, J. E., Meszaros, J. G., & Insel, P. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408704102 · Cited by 224 · see citing works
Cardiogenic Genes Expressed in Cardiac Fibroblasts Contribute to Heart Development and Repair
Furtado, M. B., Costa, M. W., Pranoto, E. A., Salimova, E., Pinto, A. R., Lam, N. T., Park, A. J., Snider, P. L., Chandran, A., Harvey, R. P., et al. (2014) · Circulation Research · doi:10.1161/circresaha.114.302530 · Cited by 214 · see citing works
Tbx20is essential for cardiac chamber differentiation and repression ofTbx2
Singh, M. K., Christoffels, V. M., Dias, J. M. M., Trowe, M., Petry, M., Schuster-Gossler, K., Bürger, A., Ericson, J., & Kispert, A. (2005) · Development · doi:10.1242/dev.01854 · Cited by 203 · see citing works
Natriuretic Peptides in the Regulation of Cardiovascular Physiology and Metabolic Events
Kerkelä, R., Ulvila, J., & Magga, J. M. (2015) · Journal of the American Heart Association · doi:10.1161/jaha.115.002423 · Cited by 172 · see citing works
Paik, D. T., Tian, L., Lee, J., Sayed, N., Chen, I. Y., Rhee, S., Rhee, J., Kim, Y., Wirka, R. C., Buikema, J. W., et al. (2018) · Circulation Research · doi:10.1161/circresaha.118.312913 · Cited by 147 · see citing works
Self-citationIyer, D., Gambardella, L., Bernard, W. G., Serrano, F., Mascetti, V. L., Pedersen, R. A., Talasila, A., & Sinha, S. (2015) · Development · doi:10.1242/dev.119271 · Cited by 137 · see citing works
Pandya, K., Kim, H., & Smithies, O. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607700103 · Cited by 120 · see citing works
Role of inflammatory cells in fibroblast activation
Hartupee, J. C., & Mann, D. L. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.11.016 · Cited by 108 · see citing works
Bao, X., Lian, X. L., Hacker, T. A., Schmuck, E. G., Qian, T., Bhute, V. J., Han, T., Shi, M., Drowley, L., Plowright, A. T., et al. (2016) · Nature Biomedical Engineering · doi:10.1038/s41551-016-0003 · Cited by 107 · see citing works
Dynamic cell–cell and cell–ECM interactions in the heart
Howard, C. M., & Baudino, T. A. (2013) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2013.10.006 · Cited by 105 · see citing works
Sacubitril/valsartan: beyond natriuretic peptides
Singh, J. S., Burrell, L. M., Cherif, M., Squire, I. B., Clark, A. L., & Lang, C. C. (2017) · Heart · doi:10.1136/heartjnl-2017-311295 · Cited by 100 · see citing works
Tcf21 regulates the specification and maturation of proepicardial cells
Tandon, P., Miteva, Y., Kuchenbrod, L. M., Cristea, I. M., & Conlon, F. L. (2013) · Development · doi:10.1242/dev.093385 · Cited by 88 · see citing works
Yan, X., Zhang, H., Fan, Q., Hu, J., Tao, R., Chen, Q., Iwakura, Y., Shen, W., Lu, L., Zhang, Q., et al. (2017) · Circulation Research · doi:10.1161/circresaha.116.310260 · Cited by 88 · see citing works
Self-citationLevick, S. P., Soto‐Pantoja, D. R., Bi, J., Hundley, W. G., Widiapradja, A., Manteufel, E. J., Bradshaw, T. W., & Meléndez, G. C. (2018) · Heart Lung and Circulation · doi:10.1016/j.hlc.2018.08.003 · Cited by 85 · see citing works
Iyer, D., Gambardella, L., Bernard, W. G., Serrano, F., Mascetti, V. L., Pedersen, R. A., Sinha, S., & Talasila, A. (2016) · Development · doi:10.1242/dev.136143 · Cited by 57 · see citing works
Horie, M., Miyashita, N., Mikami, Y., Noguchi, S. F., Yamauchi, Y., Suzukawa, M., Fukami, T., Ohta, K., Asano, Y., Sato, S., et al. (2017) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00193.2017 · Cited by 55 · see citing works
Miyoshi, T., Nakamura, K., Miura, D., Yoshida, M., Saito, Y., Akagi, S., Ohno, Y., Kondo, M., & Ito, H. (2018) · Cardiology Journal · doi:10.5603/cj.a2018.0048 · Cited by 25 · see citing works
Stem cell culture: Simply derived epicardial cells
Paik, D. T., & Wu, J. C. (2017) · Nature Biomedical Engineering · doi:10.1038/s41551-016-0015 · Cited by 3 · see citing works
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- [8]Singh MK, Christoffels VM, Dias JM, Trowe MO, Petry M, Schuster-Gossler K, Burger A, Ericson J and Kispert A. Tbx20 is essential for cardiac chamber differentiation and repression of Tbx2. Development (Cambridge, England). 2005; 132: 2697– 707. 15901664
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Cardiac fibrosis: Myofibroblast-mediated pathological regulation and drug delivery strategies
Liu, M., Abad, B. L. D. J., & Cheng, K. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.03.021 · Cited by 353 · see citing works
Li, Y., Ren, P., Dawson, A., Vasquez, H. G., Ageedi, W., Zhang, C., Luo, W., Chen, R., Li, Y., Kim, S., et al. (2020) · Circulation · doi:10.1161/circulationaha.120.046528 · Cited by 344 · see citing works
Zile, M. R., O’Meara, E., Claggett, B. L., PRESCOTT, M. F., Solomon, S. D., Swedberg, K. B., Packer, M., McMurray, J. J. V., Shi, V. C., Lefkowitz, M. P., et al. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.11.042 · Cited by 253 · see citing works
Paik, D. T., Chandy, M., & Wu, J. C. (2019) · Pharmacological Reviews · doi:10.1124/pr.116.013003 · Cited by 216 · see citing works
Self-citationZhang, W., Chen, S., Zhou, S., Wu, S., & Wang, H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.643149 · Cited by 208 · see citing works
Complex 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
SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis
Bailey, A. L., Dmytrenko, O., Greenberg, L., Bredemeyer, A. L., Ma, P., Liu, J., Penna, V., Winkler, E. S., Sviben, S., Brooks, E., et al. (2021) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2021.01.002 · Cited by 193 · see citing works
Challenges and opportunities for the next generation of cardiovascular tissue engineering
Cho, S., Discher, D. E., Leong, K. W., Vunjak-Novakovic, G., & Wu, J. C. (2022) · Nature Methods · doi:10.1038/s41592-022-01591-3 · Cited by 176 · see citing works
Self-citationA Critical Role for Estrogen-Related Receptor Signaling in Cardiac Maturation
Sakamoto, T., Matsuura, T. R., Wan, S., Ryba, D. M., Kim, J., Won, K., Lai, L., Petucci, C. J., Petrenko, N. B., Musunuru, K., et al. (2020) · Circulation Research · doi:10.1161/circresaha.119.316100 · Cited by 148 · see citing works
Multiscale Analysis of Extracellular Matrix Remodeling in the Failing Heart
Perestrelo, A. R., Silva, A. C., Cruz, J. O. L., Martino, F. D., Horváth, V., Caluori, G., Polanský, O., Vinarský, V., Azzato, G., de Marco, G., et al. (2020) · Circulation Research · doi:10.1161/circresaha.120.317685 · Cited by 124 · see citing works
Basic and Translational Research in Cardiac Repair and Regeneration
Zhang, J. J., Bolli, R., Garry, D. J., Marbán, E., Menasché, P., Zimmermann, W., Kamp, T. J., Wu, J. C., & Dzau, V. J. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.09.019 · Cited by 110 · see citing works
Self-citationAmeen, M., Sundaram, L., Shen, M., Banerjee, A., Kundu, S., Nair, S., Shcherbina, A., Gu, M., Wilson, K. D., Varadarajan, A., et al. (2022) · Cell · doi:10.1016/j.cell.2022.11.028 · Cited by 109 · see citing works
Self-citationMin, S., Kim, S., Sim, W., Choi, Y. S., Joo, H., Park, J.-H., Lee, S.-J., Kim, H., Lee, M. J., Jeong, I., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46928-y · Cited by 103 · see citing works
Cellular and Engineered Organoids for Cardiovascular Models
Thomas, D., Choi, S., Alamana, C., Parker, K. K., & Wu, J. C. (2022) · Circulation Research · doi:10.1161/circresaha.122.320305 · Cited by 95 · see citing works
Self-citationGastruloids enable modeling of the earliest stages of human cardiac and hepatic vascularization
Abilez, O. J., Yang, H., Guan, Y., Shen, M., Yıldırım, Z., Zhuge, Y., Venkateshappa, R., Zhao, S. R., Gomez, A. H., El‐Mokahal, M., et al. (2025) · Science · doi:10.1126/science.adu9375 · Cited by 99 · see citing works
Self-citationMultiscale drug screening for cardiac fibrosis identifies MD2 as a therapeutic target
Zhang, H., Thai, P. N., Shivnaraine, R. V., Ren, L., Wu, X., Siepe, D. H., Liu, Y., Tu, C., Shin, H. S., Caudal, A., et al. (2024) · Cell · doi:10.1016/j.cell.2024.09.034 · Cited by 91 · 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
Andrysiak, K., Stępniewski, J., & Dulak, J. (2021) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-021-02536-z · Cited by 90 · see citing works
Generation of human iPSCs derived heart organoids structurally and functionally similar to heart
Lee, S., Kim, Y., Son, M., Oh, M.-S., Kim, J., Ryu, B., Kang, K.-R., Baek, J., Chung, G., Woo, D. H., et al. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121860 · Cited by 80 · see citing works
Human Cardiac Organoids for Modeling Genetic Cardiomyopathy
Buono, M. F., von Boehmer, L., Strang, J., Hoerstrup, S. P., Emmert, M. Y., & Nugraha, B. (2020) · Cells · doi:10.3390/cells9071733 · Cited by 72 · 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 74 · see citing works
Self-citationCells, Materials, and Fabrication Processes for Cardiac Tissue Engineering
Montero, P., Flandes‐Iparraguirre, M., Musquiz, S., Pérez-Araluce, M., Plano, D., Sanmartín, C., Orive, G., Gavira, J. J., Prósper, F., & Mazo, M. M. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00955 · Cited by 69 · see citing works
Direct interrogation of context-dependent GPCR activity with a universal biosensor platform
Janicot, R., Maziarz, M., Park, J., Zhao, J., Luebbers, A., Green, E., Philibert, C. E., Zhang, H., Layne, M. D., Wu, J. C., et al. (2024) · Cell · doi:10.1016/j.cell.2024.01.028 · Cited by 62 · see citing works
Self-citationEngineered 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
A framework for developing sex-specific engineered heart models
Lock, R., Al Asafen, H., Fleischer, S., Tamargo, M., Zhao, Y., Radisic, M., & Vunjak-Novakovic, G. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00381-1 · Cited by 50 · see citing works
Lin, Z., Garbern, J. C., Liu, R., Li, Q., Juncosa, E. M., Elwell, H., Sokol, M. K., Aoyama, J., Deumer, U.-S., Hsiao, E., et al. (2023) · Science Advances · doi:10.1126/sciadv.ade8513 · Cited by 48 · see citing works
Hall, C., Law, J. P., Reyat, J. S., Cumberland, M. J., Hang, S., Vo, N. T. N., Raniga, K., Weston, C. J., O’Shea, C., Townend, J., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-39369-y · Cited by 49 · see citing works
Macrophages enhance contractile force in iPSC-derived human engineered cardiac tissue
Lock, R. I., Graney, P. L., Tavakol, D. N., Nash, T. R., Kim, Y., Sanchez, E., Morsink, M. A. J., Ning, D., Chen, C., Fleischer, S., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114302 · Cited by 48 · see citing works
A Call to Action for New Global Approaches to Cardiovascular Disease Drug Solutions
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Self-citationA call to action for new global approaches to cardiovascular disease drug solutions
Figtree, G. A., Broadfoot, K., Casadei, B., Califf, R. M., Crea, F., Drummond, G. R., Freedman, J. E., Guzik, T. J., Harrison, D. G., Hausenloy, D. J., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab068 · Cited by 46 · see citing works
Self-citationRecent progress of iPSC technology in cardiac diseases
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Clinical trials in-a-dish for cardiovascular medicine
Wu, X., Swanson, K., Yıldırım, Z., Liu, W., Liao, R., & Wu, J. C. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae519 · Cited by 40 · see citing works
Self-citationBrown, G. E., Han, Y. D., Michell, A. R., Ly, O. T., Vanoye, C. G., Spanghero, E., George, A. L., Darbar, D., & Khetani, S. R. (2024) · Science Advances · doi:10.1126/sciadv.adg1222 · Cited by 38 · see citing works
Lam, C. K., & Wu, J. C. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.314695 · Cited by 37 · see citing works
Self-citationBersini, S., Schulte, R. J., Huang, L., Tsai, H., & Hetzer, M. W. (2020) · eLife · doi:10.7554/elife.54383 · Cited by 32 · see citing works
GelMA hydrogel dual photo-crosslinking to dynamically modulate ECM stiffness
Smits, J. J. H. M., van der Pol, A., Goumans, M., Bouten, C. V. C., & Jorba, I. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1363525 · Cited by 32 · see citing works
Yang, P., Zhu, L., Wang, S., Gong, J., Selvaraj, J. N., Ye, L., Chen, H., Zhang, Y., Wang, G., Song, W., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52221-9 · Cited by 33 · see citing works
Self-citationNew approach methodologies for drug discovery
Liu, W., Pang, P. D., Wu, C. A., Tagle, D. A., & Wu, J. C. (2026) · Cell · doi:10.1016/j.cell.2026.02.012 · Cited by 32 · see citing works
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Reichardt, I. M., Robeson, K. Z., Regnier, M., & Davis, J. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109888 · Cited by 32 · see citing works
Hayward, K. L., Kouthouridis, S., & Zhang, B. (2020) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.0c01089 · Cited by 31 · see citing works
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Pirfenidone Has Anti-fibrotic Effects in a Tissue-Engineered Model of Human Cardiac Fibrosis
Gartner, T. C. L. B., Crnko, S., Leiteris, L., van Adrichem, I., Laake, L. W. V., Bouten, C. V. C., Goumans, M., Suyker, W. J. L., Sluijter, J. P. G., & Hjortnaes, J. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.854314 · Cited by 30 · see citing works
Examination of the role of necroptotic damage-associated molecular patterns in tissue fibrosis
Liu, X., Lu, F., & Chen, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.886374 · Cited by 29 · see citing works
Iseoka, H., Miyagawa, S., Sakai, Y., & Sawa, Y. (2021) · Stem Cell Research · doi:10.1016/j.scr.2021.102420 · Cited by 27 · see citing works
The mechanobiology of fibroblast activation in disease
Chang, Y., Lee, J. W. N., & Holle, A. W. (2025) · APL Bioengineering · doi:10.1063/5.0272393 · Cited by 29 · see citing works
Jennbacken, K., Wågberg, F., Karlsson, U., Eriksson, J., Magnusson, L. U., Chimienti, M., Ricchiuto, P., Bernström, J., Ding, M., Ross‐Thriepland, D., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20236037 · Cited by 25 · see citing works
SLIT3 deficiency attenuates pressure overload–induced cardiac fibrosis and remodeling
Gong, L., Wang, S., Shen, L., Liu, C., Shenouda, M., Li, B., Liu, X., Shaw, J. A., Wineman, A. S., Yang, Y., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.136852 · Cited by 24 · see citing works
Aminu, A. J., Petkova, M. A., Atkinson, A. J., Yanni, J., Morris, A. D., Simms, R. T., Chen, W., Yin, Z., Kuniewicz, M., Holda, M. K., et al. (2021) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2021.04.008 · Cited by 25 · see citing works
Engineering the early bone metastatic niche through human vascularized immuno bone minitissues
Colombo, M. V., Bersini, S., Arrigoni, C., Gilardi, M., Sansoni, V., Ragni, E., Candiani, G., Lombardi, G., & Moretti, M. (2021) · Biofabrication · doi:10.1088/1758-5090/abefea · Cited by 24 · see citing works
Mainardi, A., Carminati, F., Ugolini, G. S., Occhetta, P., Isu, G., Diaz, D. R., Reid, G., Visone, R., Rasponi, M., & Marsano, A. (2021) · Lab on a Chip · doi:10.1039/d1lc00092f · Cited by 24 · see citing works
Sartiani, L., Bartolucci, G., Pallecchi, M., Spinelli, V., & Cerbai, E. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.751499 · Cited by 24 · see citing works
Modulation of anti-cardiac fibrosis immune responses by changing M2 macrophages into M1 macrophages
Chen, S., Wang, K., Fan, Z., Zhou, T., Li, R., Zhang, B., Chen, J., Chi, J., Wei, K., Liu, J., et al. (2024) · Molecular Medicine · doi:10.1186/s10020-024-00858-z · Cited by 24 · see citing works
Li, Q., Wang, J., Wu, Q., Cao, N., & Yang, H. (2020) · Stem Cells Translational Medicine · doi:10.1002/sctm.19-0340 · Cited by 24 · see citing works
Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathy
Wang, B. Z., Morsink, M. A. J., Kim, S. W., Luo, L. J., Zhang, X., Soni, R. K., Lock, R. I., Rao, J., Kim, Y., Zhang, A., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci181630 · Cited by 22 · see citing works
Generation of Quiescent Cardiac Fibroblasts Derived from Human Induced Pluripotent Stem Cells
Zhang, H., Shen, M., & Wu, J. C. (2020) · Methods in molecular biology · doi:10.1007/7651_2020_300 · Cited by 23 · see citing works
Self-citationThe role of Sfrp and DKK proteins in cardiomyocyte development
Hsueh, Y., Hodgkinson, C. P., & Gomez, J. A. (2021) · Physiological Reports · doi:10.14814/phy2.14678 · Cited by 23 · see citing works
Generation of a human iPSC-derived cardiomyocyte/fibroblast engineered heart tissue model
Cumberland, M. J., Euchner, J., Azad, A. J., Vo, N. T. N., Kirchhof, P. F., Holmes, A. P., Denning, C. N., & Gehmlich, K. (2023) · F1000Research · doi:10.12688/f1000research.139482.1 · Cited by 22 · see citing works
Zhang, F., Qiu, H., Dong, X., Zhang, X., Wang, C., Li, X., Zhang, X., Na, J., Zhou, J., & Wang, C. (2022) · Life Medicine · doi:10.1093/lifemedi/lnac002 · Cited by 23 · see citing works
Fabrication of human myocardium using multidimensional modelling of engineered tissues
Montero‐Calle, P., Flandes‐Iparraguirre, M., Mountris, K. A., Nava, A., Laita, N., Rosales, R. M., Iglesias‐García, O., De‐Juan‐Pardo, E. M., Atienza, F., Fernández‐Santos, M. E., et al. (2022) · Biofabrication · doi:10.1088/1758-5090/ac8cb3 · Cited by 20 · see citing works
Yang, J., Argenziano, M., Angulo, M. B., Bertalovitz, A. C., Beidokhti, M. N., & McDonald, T. V. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.778982 · Cited by 20 · see citing works
MeCP2 inactivation of LncRNA GAS5 triggers cardiac fibroblasts activation in cardiac fibrosis
Tao, H., Shi, P., Zhao, X., Xuan, H., & Ding, X. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109705 · Cited by 18 · see citing works
Improved epicardial cardiac fibroblast generation from iPSCs
Whitehead, A. J., Hocker, J. D., Ren, B., & Engler, A. J. (2021) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2021.11.011 · Cited by 20 · see citing works
Moita, M. R., Silva, M. M., Diniz, C., Serra, M., Hoet, R., Barbas, A., & Simão, D. F. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.1015473 · Cited by 17 · see citing works
Human iPS Cell-derived Tissue Engineered Vascular Graft: Recent Advances and Future Directions
Shi, X., He, L., Zhang, S., & Luo, J. (2020) · Stem Cell Reviews and Reports · doi:10.1007/s12015-020-10091-w · Cited by 18 · see citing works
Human Induced Pluripotent Stem Cells as a Screening Platform for Drug-Induced Vascular Toxicity
Tu, C., Cunningham, N. J., Zhang, M., & Wu, J. C. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.613837 · Cited by 18 · see citing works
Self-citationThomas, D., Kim, H., Lopez, N., & Wu, J. C. (2021) · Journal of Visualized Experiments · doi:10.3791/61879 · Cited by 18 · see citing works
Self-citationDecellularized heart extracellular matrix alleviates activation of hiPSC-derived cardiac fibroblasts
Kerr, C. M., Silver, S. E., Choi, Y. S., Floy, M. E., Bradshaw, A. D., Cho, S., Palecek, S. P., & Mei, Y. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.08.023 · Cited by 17 · see citing works
Harnessing human genetics and stem cells for precision cardiovascular medicine
Caudal, A., Snyder, M. P., & Wu, J. C. (2023) · Cell Genomics · doi:10.1016/j.xgen.2023.100445 · Cited by 16 · see citing works
Self-citationFloy, M. E., Givens, S. E., Rubio, O., Mateyka, T. D., Kerr, C. M., Steinberg, A. B., Silva, A. C., Zhang, J., Mei, Y., Ogle, B. M., et al. (2021) · The FASEB Journal · doi:10.1096/fj.202100523r · Cited by 16 · see citing works
Assessment of Cardiotoxicity With Stem Cell-based Strategies
Stoter, A. M. S., Hirt, M. N., Stenzig, J., & Weinberger, F. (2020) · Clinical Therapeutics · doi:10.1016/j.clinthera.2020.08.012 · Cited by 16 · see citing works
Xiao, Y., Zhang, H., Liu, X., Xu, P., Du, H., Wang, J., Shen, J., Li, Y., Wang, Y., He, C., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58301-8 · Cited by 15 · see citing works
Self-citationEwoldt, J. K., Wang, M. C., McLellan, M. A., Cloonan, P. E., Chopra, A., Gorham, J., Li, L., DeLaughter, D. M., Gao, X., Lee, J., et al. (2024) · Science Advances · doi:10.1126/sciadv.adi6927 · Cited by 15 · see citing works
Current methods for fabricating 3D cardiac engineered constructs
Rogozinski, N., Yanez, A., Bhoi, R., Lee, M., & Yang, H. (2022) · iScience · doi:10.1016/j.isci.2022.104330 · Cited by 15 · see citing works
Micropatterned Organoids Enable Modeling of the Earliest Stages of Human Cardiac VascularizationPreprint
Abilez, O. J., Yang, H., Tian, L., Wilson, K. D., Lyall, E. H., Shen, M., Bhoi, R., Zhuge, Y., Jia, F., Wo, H.-T., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.07.08.499233 · Cited by 13 · see citing works
Self-citationDomingues, S., Darle, A., Masson, Y., Saidani, M., Lagoutte, E., Bejanariu, A., Coutier, J., Ayata, R. E., Bouschbacher, M., Peschanski, M., et al. (2022) · Cells · doi:10.3390/cells11071151 · Cited by 13 · see citing works
Martyniak, A., Jeż, M., Dulak, J., & Stępniewski, J. (2022) · IUBMB Life · doi:10.1002/iub.2685 · Cited by 13 · see citing works
Bioactive Compounds and Cardiac Fibrosis: Current Insight and Future Prospect
Majid, A., Hassan, F., Hoque, M., Gbadegoye, J., & Lebeche, D. (2023) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd10070313 · Cited by 14 · see citing works
Collagen matricryptin promotes cardiac function by mediating scar formation
Grilo, G. A., Cakir, S. N., Shaver, P. R., Iyer, R. P., Whitehead, K. M., McClung, J. M., Vahdati, A., & Brás, L. E. D. C. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121598 · Cited by 12 · see citing works
Advances in Single-Cell Multi-Omics and Application in Cardiovascular Research
Zhang, X., Qiu, H., Zhang, F., & Ding, S. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.883861 · Cited by 13 · see citing works
Deconvoluting the Cells of the Human Heart with iPSC Technology: Cell Types, Protocols, and Uses
Yu, B., Zhao, S. R., Yan, C. D., Zhang, M., & Wu, J. C. (2022) · Current Cardiology Reports · doi:10.1007/s11886-022-01670-z · Cited by 11 · see citing works
Self-citationIntegrating 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
Iglesias‐García, O., Flandes‐Iparraguirre, M., Montero‐Calle, P., Rosales, R. M., Ullate‐Agote, A., Sánchez‐Bueno, A., Larequi, E., Lusar, I. A., Laita, N., Oliván‐Viguera, A., et al. (2025) · Advanced Functional Materials · doi:10.1002/adfm.202420106 · Cited by 11 · see citing works
Wang, R., Bektik, E., Sakon, P., Wang, X., Huang, S., Meng, X., Chen, M., Han, W., Chen, J., Wang, Y., et al. (2022) · Cells · doi:10.3390/cells11172629 · Cited by 10 · see citing works
Cardiac fibrosis research: two steps forward
Fernández-Ruíz, I. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0245-7 · Cited by 10 · see citing works
Floy, M. E., Mateyka, T. D., Foreman, K. L., & Palecek, S. P. (2020) · Stem Cell Research · doi:10.1016/j.scr.2020.101831 · Cited by 10 · see citing works
Wang, E. Y., Zhao, Y., Okhovatian, S., Smith, J. B., & Radisic, M. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1005051 · Cited by 10 · see citing works
Artesunate: attenuating TLR4/MD2 signaling to alleviate cardiac fibrosis
Koch, L., Hoeft, K., & Kramann, R. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02131-z · Cited by 9 · see citing works
Mechanical stimulation of induced pluripotent stem cell derived cardiac fibroblasts
Bekedam, F. T., Smal, R., Smit, M. C., Aman, J., Noordegraaf, A. V., Bogaard, H. J., Goumans, M., de Man, F. S., & Valldeperas, A. L. (2024) · Scientific Reports · doi:10.1038/s41598-024-60102-w · Cited by 9 · see citing works
Targeting GPCRs to treat cardiac fibrosis
Zhang, H., Ren, L., & Shivnaraine, R. V. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.1011176 · Cited by 10 · see citing works
Self-citationAmeen, M., Sundaram, L., Banerjee, A., Shen, M., Kundu, S., Nair, S., Shcherbina, A., Gu, M., Wilson, K. D., Varadarajan, A., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.29.498132 · Cited by 9 · see citing works
Self-citationInduced pluripotent stem cell-based therapies for organ fibrosis
Cheng, W., Fan, C., Song, Q., Chen, P., Peng, H., Lin, L., Liu, C., Wang, B., & Zhou, Z. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1119606 · Cited by 8 · see citing works
Gartner, T. C. L. B., Wang, Y., Leiteris, L., van Adrichem, I., Marsman, J., Goumans, M., Bouten, C. V. C., Sluijter, J. P. G., den Toonder, J. M. J., Suyker, W. J. L., et al. (2023) · Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials · doi:10.1016/j.jmbbm.2023.105980 · Cited by 8 · see citing works
Wang, Y., Wu, Y., Jiang, Y., Tan, H., Guragain, B., Nguyen, T. M., Zhao, J., Zhou, Y., Nakada, Y., & Zhang, J. J. (2024) · Journal of the American Heart Association · doi:10.1161/jaha.124.037120 · Cited by 8 · see citing works
Translational insights from single-cell technologies across the cardiovascular disease continuum
van Blokland, I. V., Groot, H. E., Franke, L., van der Wijst, M. G. P., & van der Harst, P. (2021) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2021.02.009 · Cited by 8 · see citing works
Casein kinase 2 activity is a host restriction factor for AAV transduction
Kraszewska, I., Sarad, K., Andrysiak, K., Kopacz, A., Schmidt, L., Krüger, M., Dulak, J., & Jaźwa, A. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.11.010 · Cited by 8 · see citing works
Automated High-Throughput Live Cell Monitoring of Scratch Wound Closure
Schmidt, K., Lerm, D., Schmidt, A., Dickel, N., Fiedler, J., Thum, T., & Kunz, M. (2024) · Biomedical Engineering and Computational Biology · doi:10.1177/11795972241295619 · Cited by 7 · see citing works
Nagalingam, R. S., Jayousi, F., Hamledari, H., Baygi, D. H., Dababneh, S., Lindsay, C., Geltink, R. I. K., Lange, P. F., Dixon, I., Rose, R. A., et al. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1496884 · Cited by 8 · see citing works
Cheng, H., Wang, X., Qian, S.-C., Zhang, Y., Jiao, J., Zheng, B., Zhu, Y., Xu, H., Song, J., Zhang, F., et al. (2025) · Bio-Design and Manufacturing · doi:10.1631/bdm.2400168 · Cited by 7 · see citing works
Dressed in Collagen: 2D and 3D Cardiac Fibrosis Models
Cardona-Timoner, M., Gomes, R. N., & Nascimento, D. S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26073038 · Cited by 8 · see citing works
Generation of NKX2.5GFP Reporter Human iPSCs and Differentiation Into Functional Cardiac Fibroblasts
López-Muneta, L., Linares, J., Casis, Ó., Martínez-Ibáñez, L., González, A., Bezunartea, J., Nava, A., Gallego, M., Fernández‐Santos, M. E., Rodríguez-Madoz, J. R., et al. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.797927 · Cited by 7 · see citing works
- Authors
- Zhang, H., Tian, L., Shen, M., Tu, C., Wu, H., Gu, M., Paik, D. T., & Wu, J. C.
- Affiliations
- Stanford Cardiovascular Institute (US)
- Stanford Medicine (US)
- Corresponding author
- Zhang, Hao
- Tian, Lei
- Shen, Mengcheng
- Venue
- Circulation Research
- Published
- 2019-08-16
- Volume
- 125
- Issue
- 5
- Pages
- 552-566
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC6768436
- OpenAlex
- W2957473759
- Cited by
- 187
- References
- 41
- Citations by year
- 2026: 22 · 2025: 25 · 2024: 36 · 2023: 20 · 2022: 31 · 2021: 30 · 2020: 17 · 2019: 5 · 2018: 1
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (UG3TR002588, UH3TR002588)
- National Heart, Lung, and Blood Institute (K99HL133473, R00HL133473, K99HL135258, R01HL141371, R01HL145676, R01HL146690)
- National Institute of Biomedical Imaging and Bioengineering (T32EB009035)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- cardiac fibroblasts, myocardial fibrosis, induced pluripotent stem cells, quiescent fibroblasts, single-cell transcriptome, atrial natriuretic peptide, fibrogenesis
- MeSH terms
- Animals, Antifibrinolytic Agents, Cells, Cultured, Fibroblasts, Fibrosis, Humans, Myocytes, Cardiac, Mice, Induced Pluripotent Stem Cells
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