Building Advanced Cell Models for Toxicity Testing: A New Era in Drug Development

Following the FDA Modernization Act 2.0, the FDA announced plans to phase out mandatory animal testing for certain drug categories as part of a broader shift toward modern, human-relevant testing strategies.

This regulatory change opens the door for alternative approaches to be submitted in support of investigational new drug (IND) applications, marking a significant move to reduce reliance on animal models while improving predictive relevance, speeding up development timelines, and cutting costs.

Webinar Recap: Building Advanced Cell Models for Toxicity Testing

This blog summarizes highlights from the Lonza-hosted webinar “Building Advanced Cell Models for Toxicity Testing”, presented by Manisha Nautiyal, Chieh Ming Liao and Kevin Grady. The session showcased Lonza’s latest innovations in human cell-based models for toxicology, offering practical insights into how these systems can complement animal testing in line with the FDA Modernization Act 2.0.

If you missed the live event, this recap provides a comprehensive overview of the models discussed - and why they matter.
 

Liver Models: From 2D Co-Culture to 3D Spheroids

Lonza’s liver models reflect the complexity of hepatocyte–non-parenchymal cell (NPC) interactions:

• 2D Co-Culture Models: Combine hepatocytes with Kupffer cells, stellate cells, and liver endothelial cells at physiological ratios. These models maintain cell health and functionality for at least 7 days, with albumin production and cytokine release responding predictably to LPS stimulation.
• 3D Spheroid Models: PHH spheroids show stable morphology and function over 28 days. They respond to rifampicin with CYP3A4 induction and to acetaminophen with dose-dependent hepatotoxicity. Lonza’s ViaLight^® Plus Cytotoxicity BioAssay Kit enables sensitive EC50 measurements, comparable to industry standards.
• 3D Co-Culture Spheroids: Adding NPCs enhances physiological relevance and enables spheroid formation even in non- spheroid qualified hepatocyte batches. These models show robust inflammatory responses and are ideal for long-term mechanistic studies.
   

Lung Models: Air-Liquid Interface (ALI) Co-Culture

Using Lonza’s B-ALI™ Media System, bronchial epithelial cells are cultured on Transwell^® membranes and co-cultured with PBMCs in a 50/50 X-VIVO^® 15 Serum-free Hematopoietic Cell Medium and B-ALI™ Differentiation Basal Medium blend:

• The model simulates immune–epithelial interactions and mimics viral-induced inflammation, with cytokine release and epithelial thinning observed upon stimulation.
• It supports TEER, mucin, and β-tubulin staining, making it ideal for studying respiratory toxicity, immune-mediated lung damage, and diseases like COVID-19.
   

Vascular Models: Angiogenesis Assays

Lonza offers two validated angiogenesis models:

• Gel-Based Assay: A rapid, qualitative method using HUVECs and gel feeder layers. Suramin inhibits tube formation at expected doses.
• HUVEC–Fibroblast Co-Culture: A high-throughput, physiologically relevant model using dermal fibroblasts and VEGF supplementation.The model supports direct-from-cryopreservation seeding and 5-day culture with minimal handling.
   

Skin Models: Keratinocyte–Fibroblast Co-Culture

This 2D co-culture system uses matched donor keratinocytes and fibroblasts plated at a 1:3 ratio:

• Optimized culture condition supports cobblestone keratinocyte morphology and fibroblast integration.
• ICC imaging confirms interwoven layers and minimal cell death.
• Applications include skin sensitization, wound healing, and dermal toxicology in high-throughput formats.
   

Conclusion

Whether you're working on hepatotoxicity, respiratory inflammation, angiogenesis, or dermal toxicity, Lonza provides plug-and-play systems that reduce reliance on animal models while enhancing predictive accuracy.
 

Missed the webinar?

Watch the full session on demand, or contact your Lonza representative for access to protocols, data sheets, and personalized support.
Contact Scientific Support to access the webinar in Mandarin Chinese.
 

Written by 
 

Ming
Scientific Support Specialist