Porcine Models of Heart Regeneration

Swine are popular large mammals for cardiac preclinical testing due to their similarities with humans in terms of organ size and physiology. Recent studies indicate an early neonatal regenerative capacity for swine hearts similar to small mammal laboratory models such as rodents, inspiring exciting possibilities for studying cardiac regeneration with the goal of improved clinical translation to humans. However, while swine hearts are anatomically similar to humans, fundamental differences exist in growth mechanisms, nucleation, and the maturation of pig cardiomyocytes, which could present difficulties for the translation of preclinical findings in swine to human therapeutics. In this review, we discuss the maturational dynamics of pig cardiomyocytes and their capacity for proliferative cardiac regeneration during early neonatal development to provide a perspective on swine as a preclinical model for developing cardiac gene- and cell-based regenerative therapeutics.

[1]  N. Rosenthal,et al.  Getting it right: Measuring cardiomyocyte cell cycle activity and proliferation in the age of heart regeneration. , 2022, American journal of physiology. Heart and circulatory physiology.

[2]  S. Reardon First pig-to-human heart transplant: what can scientists learn? , 2022, Nature.

[3]  B. Griffith,et al.  The growth of xenotransplanted hearts can be reduced with growth hormone receptor knockout pig donors. , 2021, The Journal of thoracic and cardiovascular surgery.

[4]  J. Willerson,et al.  Gene therapy knockdown of Hippo signaling induces cardiomyocyte renewal in pigs after myocardial infarction , 2021, Science Translational Medicine.

[5]  Jianyi(Jay) Zhang,et al.  Cyclin D2 Overexpression Enhances the Efficacy of Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes for Myocardial Repair in a Swine Model of Myocardial Infarction , 2021, Circulation.

[6]  Jianyi(Jay) Zhang,et al.  Apical Resection Prolongs the Cell Cycle Activity and Promotes Myocardial Regeneration After Left Ventricular Injury in Neonatal Pig. , 2020, Circulation.

[7]  W. Pu,et al.  Cardiomyocyte Maturation: New Phase in Development. , 2020, Circulation research.

[8]  Junhyong Kim,et al.  Lamin B2 Levels Regulate Polyploidization of Cardiomyocyte Nuclei and Myocardial Regeneration. , 2020, Developmental cell.

[9]  K. Yutzey,et al.  Scar Formation with Decreased Cardiac Function Following Ischemia/Reperfusion Injury in 1 Month Old Swine , 2019, Journal of cardiovascular development and disease.

[10]  M. Krane,et al.  Agrin promotes coordinated therapeutic processes leading to improved cardiac repair in pigs , 2019, bioRxiv.

[11]  J. Molkentin,et al.  An acute immune response underlies the benefit of cardiac stem cell therapy , 2019, Nature.

[12]  Z. Bar-Joseph,et al.  Control of cytokinesis by β-adrenergic receptors indicates an approach for regulating cardiomyocyte endowment , 2019, Science Translational Medicine.

[13]  K. Yutzey,et al.  Cardiomyocyte cell cycling, maturation, and growth by multinucleation in postnatal swine , 2019, bioRxiv.

[14]  K. Yutzey,et al.  Postnatal Cardiac Development and Regenerative Potential in Large Mammals , 2019, Pediatric Cardiology.

[15]  G. Wright,et al.  Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate the Infarcted Pig Heart but Induce Ventricular Tachyarrhythmias , 2019, Stem cell reports.

[16]  Zhong Lin Wang,et al.  Symbiotic cardiac pacemaker , 2019, Nature Communications.

[17]  Fabio Bernini,et al.  MicroRNA therapy stimulates uncontrolled cardiac repair after myocardial infarction in pigs , 2019, Nature.

[18]  M. Yartsev,et al.  Evidence for hormonal control of heart regenerative capacity during endothermy acquisition , 2019, Science.

[19]  James F. Martin,et al.  The regulation and function of the Hippo pathway in heart regeneration , 2018, Wiley interdisciplinary reviews. Developmental biology.

[20]  Jianyi(Jay) Zhang,et al.  Regenerative Potential of Neonatal Porcine Hearts , 2018, Circulation.

[21]  L. Ye,et al.  Early Regenerative Capacity in the Porcine Heart , 2018, Circulation.

[22]  E. Wolf,et al.  Consistent success in life-supporting porcine cardiac xenotransplantation , 2018, Nature.

[23]  C. Mummery Perspectives on the Use of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Biomedical Research , 2018, Stem cell reports.

[24]  Davor Milicic,et al.  Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology , 2018, European journal of heart failure.

[25]  J. Møller,et al.  Large Porcine Model of Profound Acute Ischemic Cardiogenic Shock. , 2018, Methods in molecular biology.

[26]  S. Houser,et al.  Cortical Bone Stem Cell Therapy Preserves Cardiac Structure and Function After Myocardial Infarction , 2017, Circulation research.

[27]  C. Lien,et al.  Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration , 2017, Nature Genetics.

[28]  N. Bursac,et al.  The extracellular matrix protein agrin promotes heart regeneration in mice , 2017, Nature.

[29]  V. Patel,et al.  MiR‐590 Promotes Transdifferentiation of Porcine and Human Fibroblasts Toward a Cardiomyocyte‐Like Fate by Directly Repressing Specificity Protein 1 , 2016, Journal of the American Heart Association.

[30]  H. Fan,et al.  Large Mammalian Animal Models of Heart Disease , 2016, Journal of cardiovascular development and disease.

[31]  E. Porrello,et al.  Evolution, comparative biology and ontogeny of vertebrate heart regeneration , 2016, npj Regenerative Medicine.

[32]  J. Penninger,et al.  Functional Recovery of a Human Neonatal Heart After Severe Myocardial Infarction. , 2016, Circulation research.

[33]  Bin Zhou,et al.  Epicardial FSTL1 reconstitution regenerates the adult mammalian heart , 2015, Nature.

[34]  Jens R. Nyengaard,et al.  Dynamics of Cell Generation and Turnover in the Human Heart , 2015, Cell.

[35]  M. Neeman,et al.  ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation , 2015, Nature Cell Biology.

[36]  Charles E. Murry,et al.  Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate Non-Human Primate Hearts , 2014, Nature.

[37]  Filipa Pinto,et al.  Optimization of direct fibroblast reprogramming to cardiomyocytes using calcium activity as a functional measure of success. , 2013, Journal of molecular and cellular cardiology.

[38]  Dionne A. Graham,et al.  Cardiomyocyte proliferation contributes to heart growth in young humans , 2013, Proceedings of the National Academy of Sciences.

[39]  L. Zentilin,et al.  Functional screening identifies miRNAs inducing cardiac regeneration , 2012, Nature.

[40]  E. Olson,et al.  Transient Regenerative Potential of the Neonatal Mouse Heart , 2011, Science.

[41]  Samuel Bernard,et al.  Evidence for Cardiomyocyte Renewal in Humans , 2008, Science.

[42]  L. Amado,et al.  The adult Göttingen minipig as a model for chronic heart failure after myocardial infarction: focus on cardiovascular imaging and regenerative therapies. , 2008, Comparative medicine.

[43]  K. Zahka,et al.  Cardiac Recovery and Survival After Neonatal Myocardial Infarction , 1997, Pediatric Cardiology.