Dilated cardiomyopathy (DCM) is a chronic cardiac condition, primarily caused by genetic mutations affecting cardiomyocyte structure and contractility. Heart transplantation is often the last therapeutic recourse, but donor scarcity and immunosuppressive challenges necessitate alternative strategies. Cold atmospheric plasma (CAP) could be a relevant strategy to treat diseased cardiomyocytes. Indeed, CAP generates pulsed electric fields and reactive species: combining these electro-chemical properties has the potential to induce adaptive cellular remodeling and endogenous repair mechanisms leading to better survival and functionality of cardiomyocytes affected by DCM.

Our work aims to evaluate the effects of CAP on the morphology and functionality of iPSC-derived cardiomyocytes with DCM mutations, focusing on cytoskeletal organization, contractility, calcium handling, and metabolic activity.

Cardiomyocytes were generated from iPSCs derived from DCM patients and cultured into cardiac microtissues. CAP was generated using electrical discharges in ambient air, and direct/indirect treatments were both tested. Indirect treatments involved plasma-activated medium, while direct treatments applied CAP directly to the microtissues for short durations. Post-treatment analyses included tissue organization, contractility, and calcium handling.

Preliminary experiments revealed that indirect CAP treatments, using plasma-activated medium, resulted in unfavorable outcomes for cell culture due to high concentrations of reactive species compromising cell viability. Conversely, direct treatments are hypothesized to generate lower concentrations of reactive species, potentially inducing a minor intracellular stress response beneficial for cellular adaptation. Direct treatments may allow short-lived species to interact directly with the microtissues in the presence of pulsed electric fields, without significantly affecting viability. Although direct treatments have not yet been fully implemented, recent advancements vis-à-vis technical challenges suggest they hold promise for eliciting controlled stress responses conducive to cellular repair.

Indirect CAP exposure was unsuitable for cell culture, but direct CAP treatments show potential based on initial observations. Further work is required to validate these findings and refine treatment parameters. Future research will focus on implementing direct CAP treatments and evaluating their effects on cardiomyocyte functionality and survival.