Chronotropic biosensing via stem-cell derived myocyte aggregates

Biosensors play a critical role in the chronotropic regulation of rate-adaptive electronic pacemakers. However, typical pacemaker biosensors only approximate physiological function via the measurement of surrogate signals such as ventilation, and therefore can be poorly correlated with chronotropic requirements. Alternatively, the electropotential input-output relationship of cardiac myocytes could be exploited for long-term, reversible quantification of chronotropic demand by monitoring the inherent rate effects of blood-borne catecholamines. Previously, we demonstrated the utility of this approach using murine whole-heart pinnal allograft transplants. Here, we advance this technique by utilizing pluripotent embryonic stem cell-derived cardiac myocyte aggregates implanted in the pinnae of syngeneic murine hosts. After one week, in all of the aggregates that showed sustained electropotential activity, there was ≥70% concordance between the myocyte-aggregate rate and endogenous heart rate over the course of the trial, thereby demonstrating the ability of the cell-based biosensors to sense humoral signals and track endogenous chronotropic dynamics. Improvements in myocyte-aggregate electropotential competency, along with further advancements such as catheter-based myocyte-aggregate systems, may facilitate the incorporation of such long-term, reversible biosensors into cardiac pacemakers or other devices that require humoral substance sensing.