De novo establishment of an ex vivo culture for living myocardial slices applying a microphysiological system – MPSlms

Abstract Cardiovascular disease is a global health burden. To develop novel treatment options complex in vitro model systems are needed that resemble the pathophysiological situation ex vivo. Nevertheless, current pre-clinical in vitro models for pharmacological research are limited in complexity. Basic cell culture models lack cardiac tissue architecture and intercellular communication, limiting their translational capability. Force measurement methods on ex vivo cultured living myocardial slices (LMS) have been described for contraction analysis studies after compound treatment. Here, we combined LMS with a microphysiological system (MPS) to develop MPSlms as heart-on-chip approach that enables advanced nutrition circulation and integrates electrical pacing (MPSpacer) of the ex vivo cardiac tissue. To optimize the LMS technique, we designed a novel isometric tissue holder (ITH) and miniaturized the LMS format, allowing for extended condition testing and thus refinement of animal experiments. The contractile performance of cardiomyocytes was quantified by applying optical mapping of movement detection, which revealed precise and local variations in contraction within one LMS.