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Cited by 9933D Printing in Biomedical ResearchMicrofluidic and Capillary Electrophoresis ApplicationsTissue Engineering and Regenerative Medicine

A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice

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Huh, Dongeun, Leslie, Daniel C., Matthews, Benjamin D., Fraser, Jacob P., Jurek, Samuel, Hamilton, Geraldine A., Thorneloe, Kevin S., McAlexander, Michael Allen +1 more·2012·Science Translational Medicine
DOI 10.1126/scitranslmed.3004249PMC PMC8265389
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Abstract

An in vitro model of human pulmonary edema predicts drug toxicity and efficacy previously observed in humans.

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Crossref · 10.1126/scitranslmed.3004249

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  • Biomechanical stimuli such as shear stress, stretching or compression influence pathophysiological processes.

    “Biomechanical stimuli, such as shear stress, stretching or compression, influence (patho)physiological processes142–147”

    From Human disease models in drug development (2023) · cites this paper as [146]

    The Results section, “Pathological changes in barrier integrity” (page unavailable), shows that cyclic stretching during IL-2 exposure increased lung-barrier permeability and contributed to pulmonary edema. This supports stretching as an example of a biomechanical stimulus influencing a pathological process, but the cited paper does not establish the corresponding effects of shear stress or compression. (LLM, conf=0.84)

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  • Using simple, direct modulation of TRPV4 with GSK101 in a 3D microfluidic system, vascular integrity can be tuned to recapitulate known TRPV4 physiological functions in vivo, especially in pulmonary edema, and achieve vascular leakiness comparable with previous MTM studies using tumor cells.

    “Using this simple, direct modulation of TRPV4 with GSK101 in a 3D micro fl uidic system, we can therefore tune the vascular integrity to recapitulate known TRPV4 physiological functions in vivo, especially in pulmonary edema, 28,30,51,52 and achieve vascular leakiness in a manner that is comparable with previous MTM studies using tumor cells. 2,53”

    From Rapid Assessment of Nanoparticle Extravasation in a Microfluidic Tumor Model (2019) · cites this paper as [53]

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  • HUVECs may not entirely recapitulate all known roles for TRPV4 in tumor vasculature.

    “HUVECs may not entirely recapitulate all known roles for TRPV4 in tumor vasculature. 24,28,35,51,53,66”

    From Rapid Assessment of Nanoparticle Extravasation in a Microfluidic Tumor Model (2019) · cites this paper as [53]

    The Results (‘Drug testing on-chip’; page unavailable) discuss TRPV4-mediated vascular leakage in a lung model, and the Methods (‘Microfluidic cell culture’; page unavailable) identify the cells as human pulmonary microvascular endothelial cells. Searches for HUVECs and tumor vasculature found no passage addressing whether HUVECs recapitulate TRPV4’s roles in tumor vessels. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Organ chip microdevices are able to recapitulate organ-level responses to toxins, drugs, radiation, cigarette smoke, pathogens, and normal microorganisms, as well as the dependence on flow-circulating immune cells and organs to recruit specific in vitro inflammatory responses.

    “Crucially, these organ chip microdevices are able to recapitulate organ-level responses to toxins79,96,97, drugs86,98, radiation99, cigarette smoke100, pathogens96, and normal microorganisms96, as well as the dependence on flow-circulating immune cells and organs to recruit specific in vitro inflammatory responses101, which are very important for preclinical drug screening and disease modeling.”

    From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [101]

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Authors
Huh, D., Leslie, D. C., Matthews, B. D., Fraser, J. P., Jurek, S., Hamilton, G. A., Thorneloe, K. S., McAlexander, M. A., & Ingber, D. E.
Affiliations
  • Boston Children's Hospital (US)
  • Harvard University (US)
  • GlaxoSmithKline (United States) (US)
Corresponding author
Ingber, Donald E.
ORCID
Venue
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Published
2012-11-07
Volume
4
Issue
159
Pages
159ra147-159ra147
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
DOI
10.1126/scitranslmed.3004249
PMC
PMC8265389
OpenAlex
W2124838743
Cited by
993
References
45
Citations by year
2026: 38 · 2025: 41 · 2024: 77 · 2023: 81 · 2022: 95 · 2021: 110 · 2020: 100 · 2019: 80 · 2018: 76 · 2017: 92 · 2016: 65 · 2015: 37 · 2014: 61 · 2013: 36 · 2012: 3
FWCI
24.96
Type
journal article
Language
en
Open access
Locations
  • Science Translational Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Neurological Disorders and Stroke (U01NS073474)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
pulmonary edema, drug toxicity, interleukin-2, lung-on-a-chip, lung epithelial cells, pulmonary endothelial cells, mechanical strain, respiratory motion, vascular leakage, disease models, angiopoietin-1, GSK2193874, preclinical drug testing, alternatives to animal testing
MeSH terms
Animals, Biological Transport, Capillaries, Gases, Humans, Interleukin-2, Lung, Male, Mice, Inbred C57BL, Models, Biological, Pulmonary Edema, Blood-Air Barrier, Disease Progression, Microfluidic Analytical Techniques, Mice, In Vitro Techniques

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