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Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues

Author

Listed:
  • Ilya Y. Shadrin

    (Duke University)

  • Brian W. Allen

    (Duke University)

  • Ying Qian

    (Duke University)

  • Christopher P. Jackman

    (Duke University)

  • Aaron L. Carlson

    (Duke University)

  • Mark E. Juhas

    (Duke University)

  • Nenad Bursac

    (Duke University)

Abstract

Despite increased use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for drug development and disease modeling studies, methods to generate large, functional heart tissues for human therapy are lacking. Here we present a “Cardiopatch” platform for 3D culture and maturation of hiPSC-CMs that after 5 weeks of differentiation show robust electromechanical coupling, consistent H-zones, I-bands, and evidence for T-tubules and M-bands. Cardiopatch maturation markers and functional output increase during culture, approaching values of adult myocardium. Cardiopatches can be scaled up to clinically relevant dimensions, while preserving spatially uniform properties with high conduction velocities and contractile stresses. Within window chambers in nude mice, cardiopatches undergo vascularization by host vessels and continue to fire Ca2+ transients. When implanted onto rat hearts, cardiopatches robustly engraft, maintain pre-implantation electrical function, and do not increase the incidence of arrhythmias. These studies provide enabling technology for future use of hiPSC-CM tissues in human heart repair.

Suggested Citation

  • Ilya Y. Shadrin & Brian W. Allen & Ying Qian & Christopher P. Jackman & Aaron L. Carlson & Mark E. Juhas & Nenad Bursac, 2017. "Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01946-x
    DOI: 10.1038/s41467-017-01946-x
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    Cited by:

    1. 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.
    2. Yutong He & Qian Li & Pinger Chen & Qixiang Duan & Jiamian Zhan & Xiaohui Cai & Leyu Wang & Honghao Hou & Xiaozhong Qiu, 2022. "A smart adhesive Janus hydrogel for non-invasive cardiac repair and tissue adhesion prevention," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    3. Pengcheng Yang & Lihang Zhu & Shiya Wang & Jixing Gong & Jonathan Nimal Selvaraj & Lincai Ye & Hanxiao Chen & Yaoyao Zhang & Gongxin Wang & Wanjun Song & Zilong Li & Lin Cai & Hao Zhang & Donghui Zhan, 2024. "Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    4. Renjie Qiu & Xingying Zhang & Chen Song & Kaige Xu & Huijia Nong & Yi Li & Xianglong Xing & Kibret Mequanint & Qian Liu & Quan Yuan & Xiaomin Sun & Malcolm Xing & Leyu Wang, 2024. "E-cardiac patch to sense and repair infarcted myocardium," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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