Heart/liver-on-a-chip as a model for the evaluation of cardiotoxicity induced by chemotherapies

Abstract Drug discovery faces challenges due to the lack of proper preclinical tests, including conventional cell cultures and animal studies. Organ-on-a-chip devices can mimic the whole-body response to therapeutics by fluidically connecting microscale cell cultures and generating a realistic model of human organs of interest. Here, we describe a pumpless heart/liver-on-a-chip (HLC) using the HepG2 hepatocellular carcinoma cells and H9c2 rat cardiomyocytes to reproduce the cardiotoxicity induced by doxorubicin (DOX) in vitro. Cell studies confirmed the high viability of both cells up to 5 days of culture in HLC. The developed device demonstrated more significant damage to heart cells within the HLC than conventional static 3D culture in the case of DOX treatment, which is because of exposure of cells to both the parent drug and its cardiotoxic metabolite, Doxorubicinol (DOXOL). Our designed HLC device represents a unique approach to assess the off-target toxicity of drugs and their metabolites, which will eventually improve current preclinical studies.