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Challenges and opportunities for the next generation of cardiovascular tissue engineering

Abstract

Engineered cardiac tissues derived from human induced pluripotent stem cells offer unique opportunities for patient-specific disease modeling, drug discovery and cardiac repair. Since the first engineered hearts were introduced over two decades ago, human induced pluripotent stem cell-based three-dimensional cardiac organoids and heart-on-a-chip systems have now become mainstays in basic cardiovascular research as valuable platforms for investigating fundamental human pathophysiology and development. However, major obstacles remain to be addressed before the field can truly advance toward commercial and clinical translation. Here we provide a snapshot of the state-of-the-art methods in cardiac tissue engineering, with a focus on in vitro models of the human heart. Looking ahead, we discuss major challenges and opportunities in the field and suggest strategies for enabling broad acceptance of engineered cardiac tissues as models of cardiac pathophysiology and testbeds for the development of therapies.

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Fig. 1: A scatterplot depicting the trade-off between throughput and maturity in cardiac tissue engineering.
Fig. 2: Illustration of tissue maturity levels that can be achieved by current tissue engineering models.
Fig. 3: Major obstacles and opportunities in cardiac tissue engineering.

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Zixuan Zhao, Xinyi Chen, … Hanry Yu

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Acknowledgements

This work is supported by National Institutes of Health grants F32 HL152483 (to S.C.); R01 HL113006, R01 HL141371, R01 HL141851, R01 HL146690, R01 HL150693 and R01 HL163680 (to J.C.W.); and UH3 EB025765, P41 EB027062 and 3R01 HL076485 (to G.V.-N.).

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S.C. researched data, designed the figures and wrote the manuscript. S.C., D.E.D., K.W.L., G.V.-N. and J.C.W. contributed substantially to the discussion of content, and reviewed and edited the manuscript before submission.

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Correspondence to Joseph C. Wu.

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J.C.W. is a cofounder of Greenstone Biosciences and G.V.-N. is a cofounder of Tara Biosystems; however, the work presented here is independent. The other authors report no competing interests.

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Nature Methods thanks Aitor Aguirre, Milena Bellin, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Nina Vogt, in collaboration with the Nature Methods team.

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Cho, S., Discher, D.E., Leong, K.W. et al. Challenges and opportunities for the next generation of cardiovascular tissue engineering. Nat Methods 19, 1064–1071 (2022). https://doi.org/10.1038/s41592-022-01591-3

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