Microphysiological Systems Bridging Human and Animal Research: Proceedings of a Workshop—in Brief (2021) / Chapter Skim
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Microphysiological Systems: Bridging Human and Animal Research: Proceedings of a Workshop - in Brief
Microphysiological Systems: Bridging Human and Animal Research: Proceedings of a Workshop - in Brief
Pages 1-10
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The purpose of this workshop was to discuss current progress in developing MPS that realistically model in vivo animal and human physiology and to strategize about the potential to establish sustainable human and animal MPS banks.3 Speakers discussed how MPS fit within the portfolio of tools used in their fields of expertise, the limitations and areas of needed improvement for MPS, and how MPS may be used in the future as the technology develops. Presentations covered the following topics: • MPS applications in drug discovery and development, environmental hazard assessment, and basic biological research; • strategies for integrating MPS into regulatory decision making; • opportunities for bridging human and animal studies using MPS; • approaches for using in vivo and in silico model systems to optimize or augment MPS; • proposals for standardizing and sharing MPS data more broadly and across sectors; • methods for leveraging MPS to address zoonoses and fight viral pandemics; and • state-of-the-art approaches to create multi-organ MPS to recapitulate the complexity of live human and animal biology in vitro.
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derived assays, organoid/spheroid systems, and microfluidic MPS. He noted that expanded development and the use of nonhuman MPS could potentially help to replace, reduce, and refine animal use in research; evaluate environmental chemical effects on wildlife species; advance veterinary research; and bridge animal and human data, which could improve the translational, regulatory, and drug development applications of MPS data.
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Recent advances in fields such as MPS suggest the potential to replace in vivo animal models with inanimate systems for agrochemical toxicology testing. Proof-of-concept studies have, for example, shown that MPS may aid in enabling early-stage screening of compounds, potentially substituting in vivo studies for some endpoints while still allowing product developers to select the best compounds from a group of chemical analogs.
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Several panelists also emphasized the importance of developing MPS derived from animal tissues to interpret existing animal model data, to assess the ability of tissue chips to recapitulate intact in vivo organ function, and to study animal health and disease.
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MPS may also potentially contribute to replacing, reducing, and refining the use of living animal models. Such animal iPSC-derived MPS could also be used to support breakthroughs in animal health in connection with the One Health Initiative.
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For example, one vendor unexpectedly discovered that it could not ship its rat and human epithelial cell MPS in the same manner, which had significant unforeseen consequences for a project being conducted by Charles River Laboratories; any seemingly minor practical challenge could become a similarly unforeseen yet consequential issue in establishing universal MPS banks or cell banks. Panelists also noted that commercializing animal tissue MPS for veterinary health applications could contribute to the One Health Initiative's animal health objectives.
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Key challenges include establishing and maintaining mature tissue phenotypes for longer duration studies and determining how simple or complex multi-tissue models must be to adequately mimic in vivo human tissue systems. Multi-organ 3D microfluidic systems hold specific promise for modeling human chronic inflammatory diseases, which affect multiple organ systems and remain among the most difficult drug development targets, in part because they are challenging to mimic using in vivo animal models.
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MPS affiliate, which is working to leverage its large amount of in vivo animal model data to optimize MPS that consist of both human and animal cell and tissue cultures. For example, the IQ MPS affiliate is working to cross-reference animal cell–based MPS data with in vivo animal data in order to accelerate the development and validation of novel MPS technologies and applications.
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In addition to preclinical safety assessment, other applications for MPS include modeling human and animal diseases, personalized medicine, and screening patients for clinical trials, especially for cancer therapeutics, pediatric disorders, or rare diseases. Several panelists stressed that in vitro models, including MPS, can be combined with machine learning and computational modeling approaches to improve their ability to predict in vivo and clinical outcomes.
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Thiels, National Science Foundation; Sally Thompson-Iritani, University of Washington; Joseph Thulin, Medical College of Wisconsin; Patricia V Turner, Charles River Laboratories; Axel Wolff, Office of Extramural Research, Office of Laboratory Animal Welfare, NIH; and Robert H
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