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Recent advances and future prospects in direct cardiac reprogramming

Nature Cardiovascular Research volume 2, pages 1148–1158 (2023)Cite this article

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Abstract

Cardiovascular disease remains a leading cause of death worldwide despite important advances in modern medical and surgical therapies. As human adult cardiomyocytes have limited regenerative ability, cardiomyocytes lost after myocardial infarction are replaced by fibrotic scar tissue, leading to cardiac dysfunction and heart failure. To replace lost cardiomyocytes, a promising approach is direct cardiac reprogramming, in which cardiac fibroblasts are transdifferentiated into induced cardiomyocyte-like cells (iCMs). Here we review cardiac reprogramming cocktails (including transcription factors, microRNAs and small molecules) that mediate iCM generation. We also highlight mechanistic studies exploring the barriers to and facilitators of this process. We then review recent progress in iCM reprogramming, with a focus on single-cell '-omics' research. Finally, we discuss obstacles to clinical application.

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Fig. 1: Timeline of direct cardiac reprogramming.
Fig. 2: Direct reprogramming of CFs into CMs in vivo and in vitro.
Fig. 3: Barriers to and facilitators of direct cardiac reprogramming.
Fig. 4: scRNA-seq analyses of direct cardiac reprogramming.

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Acknowledgements

R.A. is supported by US National Institutes of Health (NIH) grants R01 NS112256, R01 HL148714 and R01 GM127985. Y.X. is supported by American Heart Association (AHA) grant 23POST1026377. L.Q. is supported by AHA grant 20EIA35310348 and NIH‒NHLBI grant R35HL155656.

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Authors and Affiliations

  1. McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Yifang Xie & Li Qian

  2. Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Yifang Xie & Li Qian

  3. Department of Orthopedic Surgery, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA

    Ben Van Handel

  4. Section of Cardiology, Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA

    Reza Ardehali

  5. The Texas Heart Institute, Houston, TX, USA

    Reza Ardehali

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Y.X. wrote the draft and created figures. B.V.H., L.Q. and R.A. made key edits and additions.

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Xie, Y., Van Handel, B., Qian, L. et al. Recent advances and future prospects in direct cardiac reprogramming. Nat Cardiovasc Res 2, 1148–1158 (2023). https://doi.org/10.1038/s44161-023-00377-w

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