3D InSight™ Species-Specific Toxicology Service | 3D In Vitro Liver Safety Services in preclinical models
Identification of species-specific adverse drug effects based on market-leading 3D InSight™ Liver Microtissues
Evaluate animal hepatotoxicity before in vivo testing
Species-specific liver microtissues can be used to identify potential hepatotoxicity prior to preclinical in vivo studies, supporting safer candidate selection and more efficient go/no-go decision-making.
Derisk animal findings
Species-specific liver microtissues help elucidate species differences and determine whether toxicities observed in animal studies are likely to be relevant to humans.
Our 3D InSight™ Species-Specific Toxicology platform enables assessment of hepatotoxicity across humans and animals. Derived from the preclinical models most commonly used in IND submissions, 3D InSight™ Species-Specific Liver Microtissues (LiMTs) recapitulate essential features of native liver architecture and function in a physiologically relevant 3D format.
Each microtissue is composed of carefully selected, species-specific primary hepatocytes co-cultured with non-parenchymal liver cells to mirror key hepatic functions and provide more predictive translational insights during drug safety evaluation.
Why Species-Specific Toxicology with InSphero
Standardized & Reproducible
Large, qualified lots with strict QC criteria ensure consistent, reproducible results across productions
Physiologically Relevant
Fully primary, species-specific hepatocytes and non-parenchymal cells mimic in vivo liver physiology, delivering more predictive translational data.
Single Platform, Multiple Species
Aligned human and non-human assays deliver directly comparable results, streamlining discovery of cross-species differences.
Enabling Long-Term Studies
Support up to 28-day translational toxicology studies with repeated compound applications.
Portfolio of our 3D InSight™ Species-Specific Liver Microtissues
| Rat LiMTs | Mouse LiMTs | Dog LiMTs | Monkey LiMTs | |
|---|---|---|---|---|
Strain |
Sprague-Dawley |
C57BL/6 |
Beagle |
Cynomolgus |
Hepatocytes (H) |
primary H, pooled donors |
primary H, pooled donors |
primary H, single donor |
primary H, single donor |
Non-parenchymal cells (NPC) |
crude fraction NPC, pooled donor |
crude fraction NPC, pooled donor |
crude fraction NPC, single donor |
crude fraction NPC, single donor |
Longevity |
7 days |
28 days |
28 days |
28 days |
CYP450 Activity |
Yes |
Yes |
Yes |
Yes |
Immune Activity |
No |
No |
No |
No |
Lot Validation |
Driving Translational Insights with 3D InSight™ Species-Specific Liver Microtissues
3D InSight™ Species-Specific Toxicology Service combines assays from our predictive and investigative toxicology to uncover species-dependent responses to your test items, ranging from identifying cytotoxicity across species to revealing the underlying mechanisms of liver injury to know the mechanism of liver injury.
A stark example: the fialuridine trial
Animal models often fail to predict human outcomes. The fialuridine trial proved this, no toxicity in rats, dogs, or monkeys, yet fatal liver failure in humans. 3D InSight™ Species-Specific Liver Microtissues close this gap. A 7-day ATP dose–response test clearly shows fialuridine is far more cytotoxic to 3D InSight™ Human Liver Microtissues than to animal-derived microtissues, directly mirroring the clinical outcome.
Figure legend: 7-day dose–response curve of 3D InSight™ Species-Specific Liver Microtissues treated with fialuridine. ATP measurements (mean IC₅₀ ± 95% CI) reveal human-specific cytotoxicity, aligning with in vivo findings.
Uncovering Species-Specific Mechanisms of Toxicity
3D InSight™ Specie-Specific Liver Microtissues support in-depth investigation of species-specific toxicity mechanisms through transcriptomic sequencing and mechanistic studies. Here, 3D InSight™ Rat Liver Microtissues were used to evaluate the role of cytochrome P450 (CYP450) in the cytotoxicity of aflatoxin B1, a compound known to produce a reactive toxic metabolite via hepatic CYP450 metabolism. In these microtissues, cytotoxicity of aflatoxin B1 was significantly reduced in the presence of 1-aminobenzotriazole (ABT-1), a broad-spectrum CYP450 inhibitor, revealing a mechanism of toxicity consistent with in vivo findings.
Figure legend: ATP assay and LDH assay after 7-days of Aflatoxin B1 (AFB1) treatment with or without ABT-1 treatment in 3D InSightTM Rat Liver Microtissues.
Amcenestrant: Human Safety De-risked with Liver Microtissues
Preclinical dog studies indicated Amcenestrant causes drug-induced cholestasis. Transcriptomic analysis in 3D InSight™ Human, Dog and Rat Liver Microtissues, combined with 7-day cytotoxicity assays, confirmed a dog-specific hepatotoxicity signature matching in vivo findings, while human microtissues showed no cholestasis response, indicating low risk in humans. These studies were pivotal in de-risking Amcenestrant’s clinical use as an investigational selective estrogen degrader for ER+ breast cancer, establishing mechanistic insights in vitro and validating them on existing in vivo samples, eliminating the need for additional animal testing.
Figure legend: Heatmap of Z-scores for the seven most liver-relevant pathways significantly enriched by IPA (adj. P<5.0E-03) in dog, rat, and human spheroids at 24 h for (a) amcenestrant and (b) M5 metabolite.
Adapted image form Bajaj et al., 2025
Revealing Species-Specific Responses to CAR Activation
Two studies with 3D InSight™ Human and Rat Liver Microtissues show how these models capture species differences and enable biomarker discovery. Phenobarbital activated CAR in both species, but hepatocyte proliferation occurred only in rat LiMTs, reproducing the in vivo outcome. Omics analyses further identified NPM1 and PRDX6 as rat-specific biomarkers of CAR-driven proliferation, with no comparable induction in human LiMTs. This evidence supports the regulatory goal of replacing mandatory long-term rodent cancer studies with human-relevant in vitro models and key event biomarkers for more accurate assessment of human cancer risk.
Figure legend: Representative NPM1 immunofluorescence in rat and human LiMTs. A) Phenobabital (PB) increased NPM1 expression (light blue with arrows) in rat LiMTs compared to control. B) Human LiMTs showed no NPM1 staining in either control or PB-treated samples.
Images were provided by MicroMatrices, authors of the study.
From Screening to Insights: How to get started with our Species-Specific Toxicology service
Getting started with our services is fast and easy. Choose the solution that best fits your program, ship your compounds with ease, and let our experts handle the rest. You’ll receive high-quality, actionable data in a comprehensive report designed to support confident decision-making.
Select the right assay for your program
From early-stage DILI hazard identification to advanced multi-parametric readouts, choose a solution aligned with your discovery or preclinical strategy.
Simplified compound logistics
Ship your drug candidates with ease. We coordinate logistics and prepare 3D liver microtissues in parallel to keep timelines on track.
Expert-driven In Vitro testing
Our scientific team executes your study with optimized dosing strategies, validated workflows, and robust readouts for high-confidence results.
Comprehensive, decision-ready reporting
Receive a detailed, publication-grade report with actionable insights designed to support internal reviews, regulatory submissions, and portfolio decisions.
