InSphero Study Reveals Enhanced Stress-Responsive & Metabolic Gene Expression in 3D Liver Microtissues

Publication in the Journal of Tissue Science & Engineering characterizes 3D rat liver microtissues as a beneficial organotypic model system for toxicology and compound de-risking.

Findings in a recent research article in the Journal of Tissue Science & Engineering, co-authored by InSphero AG and the University of Basel, Switzerland, provided further evidence supporting the more organotypic nature of 3D liver microtissues, and their utility as improved model systems for toxicity testing and assessment of drug-induced liver injury (DILI).

Characterizing Novel 3D Rat Liver Spheroids

The study aimed to characterize novel 3D rat liver spheroids by comparing the expression and activity of key enzymes involved in cytoprotection (Nrf2-responsive genes) and glucocorticoid metabolism (Glucocorticoid Receptor (GR)-responsive genes) in InSphero's 3D Insight™ Rat Liver Microtissues relative to traditional 2D sandwich cultures or rat hepatoma cell lines. The data revealed a distinct increase in the level and duration of expression for multiple Nrf2- and GR-responsive genes in 3D rat liver microtissues. The increased expression in 3D- versus 2D- culture was seen to persist over 3 weeks in culture, as was sustained metabolic activity of the microtissues, assessed by their ability to convert cortisone to cortisol.

Preserving Liver Gene Expression

Dr. Simon Messner, Product Manager at InSphero AG and co-author on the manuscript, stated the findings will prove beneficial to researchers looking for more long-lived toxicity models. "Currently used 2D-culture systems often fail to predict hepatotoxicity because the liver-specific gene expression is lost within 48 hours. In contrast, 3D Rat Liver Microtissues preserve liver-specific gene expression over 4 weeks in culture, which enables more predictive drug testing."

The results provide the latest insight into the more liver-like gene expression and metabolic profile of 3D microtissues, further indicating their use as a more suitable in vitro model during early-stage drug development to accurately assess and predict DILI.

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