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Updated: Dec 27, 2025
The Multi-organ Chip - A Microfluidic Platform for Long-term Multi-tissue Coculture
Published on: April 28, 2015
Drug compound screening in single and integrated multi-organoid body-on-a-chip systems
Aleksander Skardal1,2, Julio Aleman1, Steven Forsythe1
1Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27101, United States of America.
Abstract:
Current practices in drug development have led to therapeutic compounds being approved for widespread use in humans, only to be later withdrawn due to unanticipated toxicity. These occurrences are largely the result of erroneous data generated by in vivo and in vitro preclinical models that do not accurately recapitulate human physiology. Herein, a human primary cell- and stem cell-derived 3D organoid technology is employed to screen a panel of drugs that were recalled from market by the FDA. The platform is comprised of multiple tissue organoid types that remain viable for at least 28 days, in vitro. For many of these compounds, the 3D organoid system was able to demonstrate toxicity. Furthermore, organoids exposed to non-toxic compounds remained viable at clinically relevant doses. Additional experiments were performed on integrated multi-organoid systems containing liver, cardiac, lung, vascular, testis, colon, and brain. These integrated systems proved to maintain viability and expressed functional biomarkers, long-term. Examples are provided that demonstrate how multi-organoid 'body-on-a-chip' systems may be used to model the interdependent metabolism and downstream effects of drugs across multiple tissues in a single platform. Such 3D in vitro systems represent a more physiologically relevant model for drug screening and will likely reduce the cost and failure rate associated with the approval of new drugs.
Insights
This study introduces a 3D organoid model using human cells to predict drug toxicity. This advanced in vitro system accurately identifies recalled medications, improving preclinical drug screening and reducing failures.
Area of Science:
- Biomedical Engineering
- Toxicology
- Drug Development
Background:
- Current preclinical models often fail to predict human drug toxicity, leading to costly recalls.
- Inaccurate physiological representation in traditional models results in unanticipated adverse events in humans.
Purpose of the Study:
- To develop and validate a 3D organoid technology for screening drug-induced toxicity.
- To assess the predictive capability of human cell- and stem cell-derived organoids for identifying recalled pharmaceuticals.
Main Methods:
- Utilized human primary and stem cell-derived 3D organoids, maintaining viability for over 28 days in vitro.
- Screened a panel of Food and Drug Administration (FDA)-recalled drugs using various tissue organoid types.
- Developed integrated multi-organoid systems (liver, cardiac, lung, etc.) to model inter-organ drug effects.
Main Results:
- The 3D organoid system successfully identified toxicity for many recalled compounds.
- Non-toxic compounds maintained organoid viability at clinically relevant doses.
- Integrated multi-organoid systems demonstrated long-term viability and functional biomarker expression.
Conclusions:
- 3D organoid technology offers a more physiologically relevant in vitro model for drug screening.
- This platform has the potential to significantly reduce drug development costs and failure rates.
- Multi-organoid 'body-on-a-chip' systems can model complex drug metabolism and effects across multiple tissues.
