Donor-dependent reprogrammed spheroids as a new model to assess interindividual heterogeneity of drug-induced liver injury

One major drawback of preclinical models to test drug-induced liver injury (DILI) is their inability to reproduce the interindividual variability of drug responsiveness in a population. Consequently, a high number of molecules that passed preclinical phases, fail clinical trials. Using a proprietary donor-dependent cell reprogramming technology that includes intra- and inter-organ communicating molecules, we generate donor-dependent reprogrammed spheroids with distinct morphology and functionality between donors. We demonstrate that the model could recapitulate the interindividual heterogeneity of DILI effects. We show a concordance between our in vitro prediction data and clinical DILI concern drugs thus validating that donor-dependent reprogrammed spheroids are valuable models to predict clinical DILI effects in a population. Our study supports the benefit of using donor-dependent reprogrammed spheroids for hepatotoxicity evaluation in drug development and precision medicine