A DPHV-liver module recapitulates AML infiltration and chemotherapy-induced hepatotoxicity with translational utility.

Abstract

The liver is central to drug metabolism and a critical site of disease progression, making vascularized in vitro liver models essential for disease modeling, drug discovery, and mechanistic research. However, recapitulating dynamic in vivo drug responses while maintaining clinical relevance remains a major challenge for bioartificial liver systems. In acute myeloid leukemia (AML), patients frequently develop leukemic liver infiltration and chemotherapy-induced hepatotoxicity, both of which compromise therapeutic efficacy and prognosis. Human-relevant experimental models that dynamically simulate these processes are urgently needed. Here, we developed a dynamic perfusable human vascularized liver module (DPHV-LM), constructed from in vitro-expanded primary human hepatocytes within a perfusable scaffold. Perfusion of AML patient-derived cells reproduced leukemic infiltration of liver tissue. Using the DPHV-LM for drug screening and validating findings in AML mouse models, we identified ammonium glycyrrhizinate (AMGZ) as an agent that reduces cytarabine-induced hepatotoxicity and suppresses leukemic infiltration without impairing antileukemic efficacy. The hepatoprotective trends observed in the DPHV-LM were qualitatively concordant with findings from an independent retrospective clinical cohort. Collectively, these results demonstrate the transplantational potential of this platform for modeling leukemic liver pathology and for the development of hepatoprotective therapeutic strategies.