Researchers develop gene-edited stem cells to reduce arrhythmias in heart attack patients StemCellTherapy HeartDisease EngraftmentArrhythmias Cardiomyocytes Cardiac GenomeEditing PacemakerActivity Electrophysiology CellStemCell
Study: Gene editing to prevent ventricular arrhythmias associated with cardiomyocyte cell therapy. Image Credit: FrentaN / Shutterstock
So far, researchers have used mouse, rat, guinea pig, and non-human primate models of subacute MI to examine the effects of transplantation of hPSC-CMs. During normal maturation of these cells, automaticity remains limited to specialized cells in the pacemaking system, and in small animal models, high heart rates often mask EAs. However, in large animal models with heart rates comparable to humans, i.e.
About the study The authors had previously shown that hPSC CMs transplanted into the infarcted heart of a rat matured to exhibit adult-like myofibril isoform organization. This model closely mimicked the maturation milieu that hPSC-CMs would experience inside humans, thus, had more clinical and physiological relevance.
Related StoriesThe researchers characterized these hPSC-CMs in vitro and tested the impact of gene edits on EA in an in vivo model, the uninjured hearts of immunosuppressed Yucata' n minipigs, transplanted with 150 million hESC-CMs. They monitored their heart rate and rhythm with a continuous electrocardiogram system, which indicated their EA burden.
Relative to wild-type controls and the other cell lines, transplantation of post-quadruple-gene edited CMs did not result in sustained EA in vivo. Also, MEDUSA hESC-CMs engrafts were stable for three months, beat synchronously with the host myocardium, and exhibited markedly attenuated VTs. These modifications also prevented pigs' morbidity, mortality, and heart failure post-hPSC-CM transplantation.
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