Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs
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We report on a functional human model to evaluate multi-organ toxicity in a 4-organ system under continuous flow conditions in a serum-free defined medium utilizing a pumpless platform for 14 days. Computer simulations of the platform established flow rates and resultant shear stress within accepted ranges. Viability of the system was demonstrated for 14 days as well as functional activity of cardiac, muscle, neuronal and liver modules. The pharmacological relevance of the integrated modules were evaluated for their response at 7 days to 5 drugs with known side effects after a 48 hour drug treatment regime. The results of all drug treatments were in general agreement with published toxicity results from human and animal data. The presented phenotypic culture model exhibits a multi-organ toxicity response, representing the next generation of in vitro systems and constitutes a step towards an in vitro “human-on-a-chip” assay for systemic toxicity screening.
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Hickman et al. used a pumpless 4-organ system (liver, cardiac, neuronal, and muscle) to evaluate human response to five different drugs for 14 days.
“Hickman et al. took advantage of a pumpless 4-organ system (liver, cardiac, neuronal, and muscle) to evaluate the human response to five different drugs for 14 days.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [229]
This Hickman technology provided a novel tool to improve predictive ability of preclinical efficacy/toxicity studies.
“This technology provided a novel tool to improve the predictive ability of preclinical efficacy/toxicity studies229.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [229]
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Self-citationLiver–heart on chip models for drug safety
Ferrari, E., & Rasponi, M. (2021) · APL Bioengineering · doi:10.1063/5.0048986 · Cited by 53 · see citing works
Critical Considerations for the Design of Multi-Organ Microphysiological Systems (MPS)
Malik, M., Yang, Y., Fathi, P., Mahler, G. J., & Esch, M. B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.721338 · Cited by 43 · see citing works
Self-citationKang, S. G., Choi, Y. Y., Mo, S. J., Kim, T. H., Ha, J. H., Hong, D. K., Lee, H., Park, S. D., Shim, J.-J., Lee, J.-L., et al. (2023) · Nano Convergence · doi:10.1186/s40580-022-00350-6 · Cited by 37 · see citing works
- Authors
- Oleaga, C., Bernabini, C., Smith, A. S. T., Srinivasan, B., Jackson, M., McLamb, W., Platt, V., Bridges, R., Cai, Y., Santhanam, N., Berry, B., Najjar, S., Akanda, N., Guo, X., Martin, C., Ekman, G., Esch, M. B., Langer, J., Ouedraogo, G., Cotovio, J., Breton, L., Shuler, M. L., & Hickman, J. J.
- Affiliations
- University of Central Florida (US)
- Cornell University (US)
- Corresponding author
- Hickman, James J.
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-02-03
- Volume
- 6
- Issue
- 1
- Pages
- 20030-20030
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4738272
- OpenAlex
- W2394730474
- Cited by
- 442
- References
- 68
- Citations by year
- 2026: 25 · 2025: 27 · 2024: 44 · 2023: 30 · 2022: 53 · 2021: 60 · 2020: 57 · 2019: 50 · 2018: 45 · 2017: 32 · 2016: 18 · 2014: 1
- FWCI
- 23.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Journal of International Crisis and Risk Communication Research (submittedVersion)
- Funders
- National Institutes of Health (UH2TR000516)
- National Center for Advancing Translational Sciences
- 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
- multi-organ toxicity, human-on-a-chip, organ-on-a-chip, continuous flow culture, serum-free defined medium, shear stress, adverse drug reactions
- MeSH terms
- Cell Line, Cells, Cultured, Drug Evaluation, Preclinical, Humans, Liver, Models, Biological, Neurons, Culture Media, Serum-Free, Muscle Fibers, Skeletal, Coculture Techniques, Myocytes, Cardiac, Lab-On-A-Chip Devices, Hep G2 Cells, Induced Pluripotent Stem Cells
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