Impact of Transplanted hESC-derived Cardiomyocytes on Cardiac Structure and Function
To assess the impact of injected cells on cardiac structure and function, all animals received echocardiography at baseline (two days after infarction but two days prior to cell injection) and at four weeks post cardiomyocyte implantation. All animals exhibited significant cardiac dysfunction two days post infarct. On average, left-ventricular end diastolic and systolic diameters increased by 10% and 42%, respectively, and fractional shortening decreased by 40% compared to uninfarcted controls.
Four days after infarction, animals were injected with 10 million hESC-derived cardiomyocytes suspended in the survival cocktail. Animals injected with either the survival cocktail alone, serum-free media without cells, or equivalent numbers of non-cardiac hESC-derived cells suspended in the survival cocktail served as control groups.
Echocardiography performed four weeks after cell implantation showed attenuation of left-ventricular end-diastolic and end-systolic diameters in animals receiving cardiomyocytes versus all three control groups. In addition, fractional shortening was significantly improved (0.01) in animals that received cardiomyocytes compared to all three control groups. MRI analysis showed improved left-ventricular ejection fraction (p=0.05) in the cardiomyocyte-treated rats compared to controls, as well as a 2.5-fold increase in systolic wall thickening in the infarct zone relative to controls (0.01).
This study is the first to document the potential clinical utility of regenerating damaged heart muscle by injecting hESC-derived cardiomyocytes directly into the infarct zone of the heart. The survival cocktail administered with the cells enables their long-term surviva
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