Bright Ferritin for Non-Invasive MRI Monitoring of the Fate of Transplanted hPSC-Cardiomyocytes in the Infarcted Rat...

To demonstrate that a recently reported bright ferritin magnetic resonance imaging (MRI) platform can track transplanted human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) longitudinally and on-demand in the rat heart.

Ferritin-overexpressing hPSCs were differentiated into cardiomyocytes and assessed for cell viability, contractile functional proteins, and electrophysiological properties in vitro. In an immunodeficient rat model, hPSC-CMs injected into the left ventricular myocardium were tracked on cardiac MRI at 3 Tesla over 8 weeks in both healthy and infarcted hearts. Longitudinal MRI was accompanied by MnCl₂ supplementation for on-demand recall of bright signal from ferritin-overexpressing hPSC-CMs. MRI findings were corroborated against histological validation.

Ferritin-overexpressing hPSC-CMs displayed normal morphological and functional phenotypes and created viable grafts in vivo. On-demand recall of bright contrast on MRI was achieved, regardless of interval post-cell transplantation, via MnCl₂ administration to precisely map surviving hPSC-CMs in both healthy and infarcted hearts. The spatial distribution of hPSC-CMs on MRI was confirmed throughout the heart by histology. Echocardiography confirmed MnCl₂ had no impact on cardiac function, although in vitro tests revealed transiently dampened calcium handling and contractility, an effect from which cells fully recovered after removing MnCl₂.

Bright ferritin MRI allows longitudinal, non-invasive, and on-demand imaging of the distribution of viable transplanted hPSC-CMs in the healthy and infarcted rat heart.