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

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 t...

Full description

Saved in:
Bibliographic Details
Published in:Journal of personalized medicine 2021-05, Vol.11 (5), p.374
Main Authors: Biagi, Diogo, Fantozzi, Evelyn Thais, Campos-Oliveira, Julliana Carvalho, Naghetini, Marcus Vinicius, Ribeiro, Antonio Fernando, Rodrigues, Sirlene, Ogusuku, Isabella, Vanderlinde, Rubia, Christie, Michelle Lopes Araújo, Mello, Debora Bastos, de Carvalho, Antonio Carlos Campos, Valadares, Marcos, Cruvinel, Estela, Dariolli, Rafael
Format: Article
Language:English
Subjects:
Animals
Cardiac function
Cardiomyocytes
Cell cycle
Contraction
Coronary artery
Echocardiography
Heart
Heart attacks
Heart transplantation
Mortality
Myocardial infarction
Occlusion
Ostomy
Placebos
Pluripotency
Precision medicine
Stem cells
Ventricle
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2075-4426
2075-4426
DOI:10.3390/jpm11050374