Hepatoxicity SIG (Jan 25): Using human biomimetic liver microphysiology system and quantitative systems toxicology models to study MASLD and DILI-Using human biomimetic liver microphysiology system and quantitative systems toxicology models to study MASLD and DILI

Video Transcription

Video Summary

In the Hepatotoxicity Special Interest Group seminar, Dr. Larry Vernetti and Mark Medel presented their work on liver microphysiology systems (MPS) for early drug safety and precision medicine. Dr. Vernetti, an expert in drug safety from the University of Pittsburgh, focused on the application of LAMPS (Liver Acinus Microphysiology System) for predicting hepatic intrinsic clearance and hepatotoxicity. The LAMPS system utilizes a miniaturized functional unit of the liver, incorporating multiple cell types structured in an in vivo-like environment. These models are maintained under controlled conditions to predict drug-induced liver injury, analyze pharmacokinetics, and facilitate ADMET (absorption, distribution, metabolism, excretion, toxicity) studies.<br /><br />Dr. Medel, also from the University of Pittsburgh, discussed the application of these models for precision medicine, particularly in metabolic dysfunction-associated steatotic liver disease (MasLD) and its progression within the liver. A key focus was on using human biomimetic liver MPS models to examine the impact of genetic variations on disease progression and drug response. Dr. Medel highlighted their efforts to use induced pluripotent stem cells (iPSCs) to generate patient-specific liver models for mapping disease progression and evaluating therapeutic responses.<br /><br />Both speakers emphasized the potential of these advanced liver models for improving drug safety testing, preclinical trials, and the precision medicine approach by identifying patient-specific responses through integrating computational simulation tools with in vitro data, highlighting the importance of a multidisciplinary approach.

Keywords

Hepatotoxicity

Liver Microphysiology Systems

LAMPS

Hepatic Intrinsic Clearance

Drug-Induced Liver Injury

ADMET Studies

Precision Medicine

Metabolic Dysfunction-Associated Steatotic Liver Disease

Induced Pluripotent Stem Cells

Patient-Specific Models

Multidisciplinary Approach