AAV-mediated reprogramming of stem cell-derived cardiomyocytes could act as biological pacemaker

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A collaborative research led by scientists at Sweden’s Karolinska Institute have used recombinant adeno-associated viral (AAV) vector to reprogram human pluripotent stem cell (hPSC)-derived ventricular cardiomyocytes into pacemaker cardiomyocytes.

Electronic pacemakers are the current treatment option to control abnormal heart rhythms. However, the maintenance they require and the associated risk of complications have motivated research on biological alternatives. Various cell and gene-based approaches are being tested to achieve this goal. The most recent approach has been the use of pluripotent stem cells derived from adult cells and to differentiate them into a cardiogenic lineage, thus rasing the possibility of an autologous approach to biological pacing.

In the present study published in Biochemical and Biophysical research communications, a research team led by Dr Ronald Li used AAV-mediated gene transfer to convert hPSC-derived ventricular cardiomyocytes to pacemaker cardiomyocytes. AAV9 vector encoding the gene for a hyperpolarization-activated cation channel protein, HCN1, was used in the study. The pacemaker cardiomyocytes generated through this method showed automaticity and action potential parameters typical of native nodal pacemaker cardiomyocytes. More importantly, implantation of the newly generated pacemaker cardiomyocytes in a preclinical porcine model of complete heart block significantly reduced the dependence on device-supported pacing and generated spontaneous heart rhythms. Findings from this study further supports the use of a cell-based biological pacemaker.

Although advances in the field provide optimism for future clinical translation, many challenges for instance, risk of cell migration and insufficient duration of pacemaker function, need addressing before clinical translation.

Source: AAV-mediated conversion of human pluripotent stem cell-derived pacemaker. Chan PKW et al., Biochemical and Biophysical research communications, October 2017. DOI