Perfused Human Liver Module for AML Infiltration and Cytarabine Injury

Research Applications

Short-term assessment of disease-context hepatotoxicity and candidate hepatoprotection during AML chemotherapy.

Model & Design

Expanded primary human hepatocytes and HUVEC vasculature with AML bone-marrow mononuclear cells from three donors. The hepatic compartment includes decellularized liver matrix.

Experimental Format

Printed perfused construct compared with static 3D culture; seven-day structural/function characterization, infiltration time course and 12-hour drug comparisons.

Model Components

• Component

  Biological compartments

  Description

  ProliHH hepatocytes, HUVECs and patient AML cells. One AML donor supplied the infiltration time course and two additional donors supplied further comparisons.

• Component

  Measurements and controls

  Description

  Perfused versus static culture; cytarabine with or without AMGZ or other candidate protectants. Viability, albumin, CYP1A2/3A4, caspase-3 and leukemic infiltration; isolated AML assays and separate mouse/retrospective cohorts.

Measurements & Endpoints

• Hepatocyte viability, albumin and CYP activity
• Leukemic infiltration
• Caspase-3-associated injury
• Cell-state and CDA expression
• Separate mouse liver burden and overall survival

Analysis

Evaluate hepatic protection and infiltration within the construct, then compare AMGZ effects on isolated AML cells. Treat local cytarabine stabilization as a proposed mechanism and clinical cohort trajectories as separate associations.

Published Evidence

• Study Sample

  Three AML donor samples; retrospective cohort 422 patients, including 326 with normal baseline function and 313 receiving cytarabine plus AMGZ for serial-marker analysis.

  Comparison

  Static culture, drug-only/untreated conditions, other protectants, isolated AML cells and separate xenograft comparisons.

  Finding

  AMGZ reduced hepatic injury and infiltration without significant direct apoptosis/migration/invasion effects in isolated AML cells. Mouse hepatic outcomes improved, but extrahepatic burden and overall survival did not improve significantly relative to the stated cytarabine comparison.

  Interpretation & Limits

  • Seven-day model lacks Kupffer and stellate cells and full sinusoidal architecture.
  • Reduced CDA expression does not directly measure local cytarabine exposure.
  • Retrospective marker improvement lacks randomization and spontaneous-recovery controls; individual patient prediction was not tested.

  Study Design

  Primary study comparisons of the stated models, treatments and measurements.