AI Article Synopsis
- Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) show potential for heart regeneration, particularly in pig hearts after injury.
- Transplanting these immature cells led to significant heart tissue development, good integration with host vasculature, and low rejection levels.
- However, the study observed frequent ventricular tachycardia in pigs receiving hESC-CMs, suggesting complex electrical activity patterns that need further research to understand their mechanisms.
Article Abstract
Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) show considerable promise for regenerating injured hearts, and we therefore tested their capacity to stably engraft in a translationally relevant preclinical model, the infarcted pig heart. Transplantation of immature hESC-CMs resulted in substantial myocardial implants within the infarct scar that matured over time, formed vascular networks with the host, and evoked minimal cellular rejection. While arrhythmias were rare in infarcted pigs receiving vehicle alone, hESC-CM recipients experienced frequent monomorphic ventricular tachycardia before reverting back to normal sinus rhythm by 4 weeks post transplantation. Electroanatomical mapping and pacing studies implicated focal mechanisms, rather than macro-reentry, for these graft-related tachyarrhythmias as evidenced by an abnormal centrifugal pattern with earliest electrical activation in histologically confirmed graft tissue. These findings demonstrate the suitability of the pig model for the preclinical development of a hESC-based cardiac therapy and provide new insights into the mechanistic basis of electrical instability following hESC-CM transplantation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524945 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2019.04.005 | DOI Listing |
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