Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform
Open accessAbstract
Many drugs have progressed through preclinical and clinical trials and have been available – for years in some cases – before being recalled by the FDA for unanticipated toxicity in humans. One reason for such poor translation from drug candidate to successful use is a lack of model systems that accurately recapitulate normal tissue function of human organs and their response to drug compounds. Moreover, tissues in the body do not exist in isolation, but reside in a highly integrated and dynamically interactive environment, in which actions in one tissue can affect other downstream tissues. Few engineered model systems, including the growing variety of organoid and organ-on-a-chip platforms, have so far reflected the interactive nature of the human body. To address this challenge, we have developed an assortment of bioengineered tissue organoids and tissue constructs that are integrated in a closed circulatory perfusion system, facilitating inter-organ responses. We describe a three-tissue organ-on-a-chip system, comprised of liver, heart, and lung, and highlight examples of inter-organ responses to drug administration. We observe drug responses that depend on inter-tissue interaction, illustrating the value of multiple tissue integration for in vitro study of both the efficacy of and side effects associated with candidate drugs.
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Microfluidic systems can link different organs-on-a-chip to potentially simulate the complexity of multiorgan drug metabolism and pharmacokinetics.
“Furthermore, microfluidic systems can link different organs-on-a-chip to potentially simulate the complexity of multiorgan drug metabolism and pharmacokinetics9,47,50,68–71.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [70]
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- Authors
- Skardal, A., Murphy, S. V., Devarasetty, M., Mead, I., Kang, H.-W., Seol, Y.-J., Shrike Zhang, Y., Shin, S.-R., Zhao, L., Aleman, J., Hall, A. R., Shupe, T. D., Kleensang, A., Dokmeci, M. R., Jin Lee, S., Jackson, J. D., Yoo, J. J., Hartung, T., Khademhosseini, A., Soker, S., Bishop, C. E., & Atala, A.
- Affiliations
- Virginia Tech - Wake Forest University School of Biomedical Engineering & Sciences (US)
- Wake Forest University Health Sciences (US)
- Brigham and Women's Hospital (US)
- Johns Hopkins University (US)
- Corresponding author
- Skardal, Aleksander
- Atala, Anthony
- ORCID
- Venue
- Scientific Reports
- Published
- 2017-08-18
- Volume
- 7
- Issue
- 1
- Pages
- 8837-8837
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5562747
- OpenAlex
- W2746127474
- Cited by
- 623
- References
- 54
- Citations by year
- 2026: 59 · 2025: 72 · 2024: 74 · 2023: 64 · 2022: 91 · 2021: 94 · 2020: 66 · 2019: 56 · 2018: 40 · 2017: 5 · 2014: 1
- FWCI
- 20.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- KOPS (University of Konstanz) (submittedVersion, cc-by)
- Scholarworks@UNIST (Ulsan National Institute of Science and Technology) (submittedVersion, cc-by)
- VTechWorks (Virginia Tech) (submittedVersion, cc-by)
- Funders
- Wake Forest University (P30 CA012197, NCI CCSG P30CA012197)
- Defense Threat Reduction Agency (N6601‐13‐C‐2027)
- National Cancer Institute (NCI CCSG P30CA012197, CCSG P30CA012197, P30CA012197)
- National Institute of Biomedical Imaging and Bioengineering (T32EB014836)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- organ-on-a-chip, liver, heart, lung, organoids, drug toxicity, adverse drug reactions, in vitro drug testing
- MeSH terms
- Equipment Design, Heart, Humans, Liver, Lung, Organoids, Microfluidics, Tissue Array Analysis, Drug Discovery, Lab-On-A-Chip Devices
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