Summary
This paper presents PEGASO, an integrated multi-organ-on-a-chip platform designed to address limitations in current drug development pipelines by providing a more physiologically complex human preclinical model. The system comprises five fluidically connected units hosting human primary cells and iPSC-derived cells representing key organs and barriers relevant to drug absorption, metabolism, and neurological effects. Validation with donepezil demonstrates the platform's potential to better predict in vivo drug responses and reduce reliance on traditional animal models.
UK applicability
The platform is relevant to UK pharmaceutical development and regulatory frameworks (MHRA, EMA) seeking alternatives to animal testing. The system could support UK-based drug development pipelines and contribute to 3Rs (Replacement, Reduction, Refinement) objectives in preclinical research.
Key measures
Multi-organ system integration; human cell culture dynamics; drug response modelling; biological feature recapitulation across gut-brain axis and liver tissues
Outcomes reported
The study developed and characterised the PEGASO multi-organ-on-a-chip platform, which integrates five connected units harbouring human primary cells and iPSC-derived cells representing the gut, immune system, liver, blood-brain barrier, and brain. The platform was challenged with donepezil to demonstrate its capability for drug testing applications.
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