Abstract
The transplantation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) has garnered significant attention as a potential means of restoring lost muscle mass and contractile function in injured hearts. Early preclinical work with hPSC-CMs employed rodent models, but the field has recently advanced to transplantation studies in more translationally relevant large animal models including non-human primates and swine. The pig is a particularly attractive model for such studies because the size, structure, and physiology of the porcine heart is very similar to that of humans. The pig model has reasonably high throughput, is readily amenable to clinically available cell delivery methods and imaging modalities and has been used frequently to test the safety and efficacy of new cardiac therapies. Here, we describe methods that were established in our laboratory for the specific purpose of testing hPSC-CM transplantation in a pig model of subacute myocardial infarction, but these same techniques should be broadly applicable to the transepicardial delivery of other biologicals including other candidate cell populations, biomaterials, and/or viral vectors.
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References
Virani SS, Alonso A, Benjamin EJ et al (2020) Heart disease and stroke statistics—2020 update: a report from the American Heart Association. Circulation 141:139–596
Laflamme MA, Murry CE (2011) Heart regeneration. Nature 473:326–335
Romagnuolo R, Laflamme MA (2017) Programming cells for cardiac repair. Curr Opin Biotechnol 47:43–50
Laflamme MA, Chen KY, Naumova AV et al (2007) Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 25:1015–1024
Caspi O, Huber I, Kehat I et al (2007) Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol 50:1884–1893
Shiba Y, Fernandes S, Zhu W-Z et al (2012) Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts. Nature 489:322–325
Shiba Y, Filice D, Fernandes S et al (2014) Electrical integration of human embryonic stem cell-derived cardiomyocytes in a Guinea Pig chronic infarct model. J Cardiovasc Pharmacol Ther 19:368–381
van Laake LW, Passier R, Doevendans PA, Mummery CL (2008) Human embryonic stem cell–derived cardiomyocytes and cardiac repair in rodents. Circ Res 102:1008–1010
Chong JJH, Yang X, Don CW et al (2014) Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature 510:273–277
Shiba Y, Gomibuchi T, Seto T et al (2016) Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts. Nature 538:388–391
Liu Y-W, Chen B, Yang X et al (2018) Human embryonic stem cell-derived cardiomyocytes restore function in infarcted hearts of non-human primates. Nat Biotechnol 36:597–605
Romagnuolo R, Masoudpour H, Porta-Sánchez A et al (2019) Human embryonic stem cell-derived cardiomyocytes regenerate the infarcted pig heart but induce ventricular tachyarrhythmias. Stem Cell Rep 12:967–981
Wessels A, Sedmera D (2003) Developmental anatomy of the heart: a tale of mice and man. Physiol Genomics 15:165–176
Malinow MR, Hill JD, Ochsner AJ (1977) Heart rate in caged Macaca fascicularis. Effects of short-term physical exercise. J Med Primatol 6:69–75
Hughes HC (1986) Swine in cardiovascular research. Lab Anim Sci 36:348–350
Lelovas PP, Kostomitsopoulos NG, Xanthos TT (2014) A comparative anatomic and physiologic overview of the porcine heart. J Am Assoc Lab Anim Sci 53:432–438
Ghugre NR, Ramanan V, Pop M et al (2011) Quantitative tracking of edema, hemorrhage, and microvascular obstruction in subacute myocardial infarction in a porcine model by MRI: quantitative tracking of edema, hemorrhage, and MVO. Magn Reson Med 66:1129–1141
Michael Swindle M, Smith AC (2008) Swine in biomedical research. In: Conn PM (ed) Sourcebook of models for biomedical research. Humana Press, Totowa, NJ, pp 233–239
Koudstaal S, Jansen MS, Lorkeers S, Gho JMIH et al (2014) Myocardial infarction and functional outcome assessment in pigs. J Vis Exp 86:e51269
Acknowledgments
This work was supported by funding from an Ontario Institute for Regenerative Medicine Disease Team award, the McEwen Stem Cell Institute, the Peter Munk Cardiac Centre, the John R. Evans Leaders Fund/Canada Foundation for Innovation, and the University of Toronto’s Medicine by Design initiative, which receives funding from the Canada First Research Excellence Fund. The authors would also like to thank Alyssa Goldstein and Karen Ho for their technical expertise and invaluable assistance with the preparation of this manuscript, and Christoph Haller for helpful comments.
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Wulkan, F., Romagnuolo, R., Qiang, B., Laflamme, M.A. (2022). Methods for Transepicardial Cell Transplantation in a Swine Myocardial Infarction Model. In: Coulombe, K.L., Black III, L.D. (eds) Cardiac Tissue Engineering. Methods in Molecular Biology, vol 2485. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2261-2_13
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DOI: https://doi.org/10.1007/978-1-0716-2261-2_13
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