Global Preclinical Safety, AbbVie Inc, North Chicago, IL, USA.
National Toxicology Program, The National Institute of Environmental Health Sciences, Durham, NC, USA.
Vet Pathol. 2020 May;57(3):358-368. doi: 10.1177/0300985820908794. Epub 2020 Mar 17.
High-throughput in vitro models lack human-relevant complexity, which undermines their ability to accurately mimic in vivo biologic and pathologic responses. The emergence of microphysiological systems (MPS) presents an opportunity to revolutionize in vitro modeling for both basic biomedical research and applied drug discovery. The MPS platform has been an area of interdisciplinary collaboration to develop new, predictive, and reliable in vitro methods for regulatory acceptance. The current MPS models have been developed to recapitulate an organ or tissue on a smaller scale. However, the complexity of these models (ie, including all cell types present in the in vivo tissue) with appropriate structural, functional, and biochemical attributes are often not fully characterized. Here, we provide an overview of the capabilities and limitations of the microfluidic MPS model (aka organs-on-chips) within the scope of drug development. We recommend the engagement of pathologists early in the MPS design, characterization, and validation phases, because this will enable development of more robust and comprehensive MPS models that can accurately replicate normal biology and pathophysiology and hence be more predictive of human responses.
高通量体外模型缺乏与人类相关的复杂性，这降低了它们准确模拟体内生物学和病理学反应的能力。微生理系统 (MPS) 的出现为基础生物医学研究和应用药物发现中的体外建模带来了革命性的变化。MPS 平台一直是跨学科合作的一个领域，旨在开发新的、可预测的和可靠的体外方法以获得监管部门的认可。目前已经开发出了多种 MPS 模型，以在更小的规模上重现器官或组织。然而，这些模型的复杂性（即包括体内组织中存在的所有细胞类型）及其适当的结构、功能和生化特性通常并未完全得到表征。在这里，我们概述了微流控 MPS 模型（又名器官芯片）在药物开发范围内的功能和局限性。我们建议病理学家尽早参与 MPS 的设计、表征和验证阶段，因为这将使开发出更强大和全面的 MPS 模型成为可能，这些模型可以准确地复制正常生物学和病理生理学，从而更能预测人体的反应。
