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Advanced maturation of human cardiac tissue grown from pluripotent stem cells

Author

Listed:
  • Kacey Ronaldson-Bouchard

    (Columbia University)

  • Stephen P. Ma

    (Columbia University)

  • Keith Yeager

    (Columbia University)

  • Timothy Chen

    (Columbia University)

  • LouJin Song

    (Columbia University)

  • Dario Sirabella

    (Columbia University)

  • Kumi Morikawa

    (Columbia University)

  • Diogo Teles

    (Columbia University
    University of Minho
    ICVS/3B’s, PT Government Associate Laboratory)

  • Masayuki Yazawa

    (Columbia University)

  • Gordana Vunjak-Novakovic

    (Columbia University
    Columbia University)

Abstract

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.

Suggested Citation

  • Kacey Ronaldson-Bouchard & Stephen P. Ma & Keith Yeager & Timothy Chen & LouJin Song & Dario Sirabella & Kumi Morikawa & Diogo Teles & Masayuki Yazawa & Gordana Vunjak-Novakovic, 2018. "Advanced maturation of human cardiac tissue grown from pluripotent stem cells," Nature, Nature, vol. 556(7700), pages 239-243, April.
  • Handle: RePEc:nat:nature:v:556:y:2018:i:7700:d:10.1038_s41586-018-0016-3
    DOI: 10.1038/s41586-018-0016-3
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    Cited by:

    1. Bas Loo & Simone A. Den & Nuno Araújo-Gomes & Vincent Jong & Rebecca R. Snabel & Maik Schot & José M. Rivera-Arbeláez & Gert Jan C. Veenstra & Robert Passier & Tom Kamperman & Jeroen Leijten, 2023. "Mass production of lumenogenic human embryoid bodies and functional cardiospheres using in-air-generated microcapsules," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Ian Fernandes & Shunsuke Funakoshi & Homaira Hamidzada & Slava Epelman & Gordon Keller, 2023. "Modeling cardiac fibroblast heterogeneity from human pluripotent stem cell-derived epicardial cells," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Quanxia Lyu & Shu Gong & Jarmon G. Lees & Jialiang Yin & Lim Wei Yap & Anne M. Kong & Qianqian Shi & Runfang Fu & Qiang Zhu & Ash Dyer & Jennifer M. Dyson & Shiang Y. Lim & Wenlong Cheng, 2022. "A soft and ultrasensitive force sensing diaphragm for probing cardiac organoids instantaneously and wirelessly," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. Mao Mao & Xiaoli Qu & Yabo Zhang & Bingsong Gu & Chen Li & Rongzhi Liu & Xiao Li & Hui Zhu & Jiankang He & Dichen Li, 2023. "Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Gaspard Pardon & Alison S. Vander Roest & Orlando Chirikian & Foster Birnbaum & Henry Lewis & Erica A. Castillo & Robin Wilson & Aleksandra K. Denisin & Cheavar A. Blair & Colin Holbrook & Kassie Kole, 2024. "Tracking single hiPSC-derived cardiomyocyte contractile function using CONTRAX an efficient pipeline for traction force measurement," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    6. Sungjin Min & Suran Kim & Woo-Sup Sim & Yi Sun Choi & Hyebin Joo & Jae-Hyun Park & Su-Jin Lee & Hyeok Kim & Mi Jeong Lee & Inhea Jeong & Baofang Cui & Sung-Hyun Jo & Jin-Ju Kim & Seok Beom Hong & Yeon, 2024. "Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    7. Mariana A. Branco & Tiago P. Dias & Joaquim M. S. Cabral & Perpetua Pinto-do-Ó & Maria Margarida Diogo, 2022. "Human multilineage pro-epicardium/foregut organoids support the development of an epicardium/myocardium organoid," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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