Human embryonic stem cell-derived cardiomyocytes restore function in infarcted hearts of non-human primates

Area of Science:

• Cardiology
• Regenerative Medicine
• Stem Cell Biology

Background:

• Pluripotent stem cell-derived cardiomyocytes offer potential for myocardial repair.
• Previous studies showed efficacy in smaller animal models.
• The efficacy and safety in large animal models remained largely unknown.

Purpose of the Study:

• To evaluate the efficacy of human embryonic stem cell-derived cardiomyocyte (hESC-CM) transplantation in restoring cardiac function in a large animal model of myocardial infarction.
• To assess the functional integration and potential arrhythmogenic risks of hESC-CM grafts.

Main Methods:

• Cryopreserved hESC-CMs (approximately 750 million) were transplanted into macaques with induced myocardial infarctions.
• Cardiac function was assessed using global left ventricular ejection fraction measurements.
• Graft integration, cell survival, and electrophysiological properties were evaluated using histological analysis and electrical mapping.

Main Results:

• hESC-CM transplantation significantly improved left ventricular ejection fraction compared to controls at 1 and 3 months post-transplantation.
• Grafts successfully integrated with host tissue, forming electromechanical junctions and comprising predominantly ventricular myocytes by 3 months.
• A subset of animals experienced ventricular arrhythmias, originating from ectopic pacemakers within the grafts.

Conclusions:

• Transplantation of hESC-CMs can durably improve cardiac function in a large animal model with myocardial infarction.
• The study demonstrates successful remuscularization and functional integration of human cardiomyocytes.
• Graft-associated arrhythmias are a potential concern that requires further investigation and management strategies.