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Postnatal Cardiac Development and Regenerative Potential in Large Mammals

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Abstract

The neonatal capacity for cardiac regeneration in mice is well studied and has been used to develop many potential strategies for adult cardiac regenerative repair following injury. However, translating these findings from rodents to designing regenerative therapeutics for adult human heart disease remains elusive. Large mammals including pigs, dogs, and sheep are widely used as animal models of humans in preclinical trials of new cardiac drugs and devices. However, very little is known about the fundamental cardiac cell biology and the timing of postnatal cardiac events that influence cardiomyocyte proliferation in these animals. There is emerging evidence that external physiological and environmental cues could be the key to understanding cardiomyocyte proliferative behavior. In this review, we survey available literature on postnatal development in various large mammal models to offer a perspective on the physiological and cellular characteristics that could be regulating cardiomyocyte proliferation. Similarities and differences between developmental milestones, cardiomyocyte maturational events, as well as environmental cues regulating cardiac development, are discussed for various large mammals, with a focus on postnatal cardiac regenerative potential and translatability to the human heart.

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Acknowledgements

We thank members of the Yutzey lab for valuable input and discussion.

Funding

This study was funded by NIH R01HL135848, R01HL142217, and Cincinnati Children’s Research Foundation.

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Authors and Affiliations

  1. Division of Molecular Cardiovascular Biology, The Heart Institute, Cincinnati Children’s Hospital Medical Center, ML7020, 240 Albert Sabin Way, Cincinnati, OH, 45229, USA

    Nivedhitha Velayutham, Emma J. Agnew & Katherine E. Yutzey

  2. Molecular and Developmental Biology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Nivedhitha Velayutham & Katherine E. Yutzey

  3. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Katherine E. Yutzey

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  1. Nivedhitha Velayutham
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  2. Emma J. Agnew
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  3. Katherine E. Yutzey
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Correspondence to Katherine E. Yutzey.

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Velayutham, N., Agnew, E.J. & Yutzey, K.E. Postnatal Cardiac Development and Regenerative Potential in Large Mammals. Pediatr Cardiol 40, 1345–1358 (2019). https://doi.org/10.1007/s00246-019-02163-7

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