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Article

In Situ Maturated Early-Stage Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improve Cardiac Function by Enhancing Segmental Contraction in Infarcted Rats

1
PluriCell Biotech, São Paulo 05508-000, Brazil
2
Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, 81377 München, Germany
3
Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
4
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
*
Author to whom correspondence should be addressed.
These authors equally contributed to this work.
Academic Editor: Aitor Aguirre
J. Pers. Med. 2021, 11(5), 374; https://doi.org/10.3390/jpm11050374
Received: 17 March 2021 / Revised: 21 April 2021 / Accepted: 30 April 2021 / Published: 4 May 2021
The scant ability of cardiomyocytes to proliferate makes heart regeneration one of the biggest challenges of science. Current therapies do not contemplate heart re-muscularization. In this scenario, stem cell-based approaches have been proposed to overcome this lack of regeneration. We hypothesize that early-stage hiPSC-derived cardiomyocytes (hiPSC-CMs) could enhance the cardiac function of rats after myocardial infarction (MI). Animals were subjected to the permanent occlusion of the left ventricle (LV) anterior descending coronary artery (LAD). Seven days after MI, early-stage hiPSC-CMs were injected intramyocardially. Rats were subjected to echocardiography pre-and post-treatment. Thirty days after the injections were administered, treated rats displayed 6.2% human cardiac grafts, which were characterized molecularly. Left ventricle ejection fraction (LVEF) was improved by 7.8% in cell-injected rats, while placebo controls showed an 18.2% deterioration. Additionally, cell-treated rats displayed a 92% and 56% increase in radial and circumferential strains, respectively. Human cardiac grafts maturate in situ, preserving proliferation with 10% Ki67 and 3% PHH3 positive nuclei. Grafts were perfused by host vasculature with no evidence for immune rejection nor ectopic tissue formations. Our findings support the use of early-stage hiPSC-CMs as an alternative therapy to treat MI. The next steps of preclinical development include efficacy studies in large animals on the path to clinical-grade regenerative therapy targeting human patients. View Full-Text
Keywords: stem cell-therapy; human induced pluripotent stem cells; cardiomyocytes; myocardial infarction; heart failure; regeneration; cardiac function stem cell-therapy; human induced pluripotent stem cells; cardiomyocytes; myocardial infarction; heart failure; regeneration; cardiac function
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MDPI and ACS Style

Biagi, D.; Fantozzi, E.T.; Campos-Oliveira, J.C.; Naghetini, M.V.; Ribeiro, A.F., Jr.; Rodrigues, S.; Ogusuku, I.; Vanderlinde, R.; Christie, M.L.A.; Mello, D.B.; de Carvalho, A.C.C.; Valadares, M.; Cruvinel, E.; Dariolli, R. In Situ Maturated Early-Stage Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improve Cardiac Function by Enhancing Segmental Contraction in Infarcted Rats. J. Pers. Med. 2021, 11, 374. https://doi.org/10.3390/jpm11050374

AMA Style

Biagi D, Fantozzi ET, Campos-Oliveira JC, Naghetini MV, Ribeiro AF Jr., Rodrigues S, Ogusuku I, Vanderlinde R, Christie MLA, Mello DB, de Carvalho ACC, Valadares M, Cruvinel E, Dariolli R. In Situ Maturated Early-Stage Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improve Cardiac Function by Enhancing Segmental Contraction in Infarcted Rats. Journal of Personalized Medicine. 2021; 11(5):374. https://doi.org/10.3390/jpm11050374

Chicago/Turabian Style

Biagi, Diogo, Evelyn T. Fantozzi, Julliana C. Campos-Oliveira, Marcus V. Naghetini, Antonio F. Ribeiro Jr., Sirlene Rodrigues, Isabella Ogusuku, Rubia Vanderlinde, Michelle L.A. Christie, Debora B. Mello, Antonio C.C. de Carvalho, Marcos Valadares, Estela Cruvinel, and Rafael Dariolli. 2021. "In Situ Maturated Early-Stage Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improve Cardiac Function by Enhancing Segmental Contraction in Infarcted Rats" Journal of Personalized Medicine 11, no. 5: 374. https://doi.org/10.3390/jpm11050374

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