Human biomimetic liver microphysiology systems in drug development and precision medicine.
Human biomimetic liver microphysiology systems in drug development and precision medicine.
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DOI：
10.1038/s41575-020-00386-1
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发表时间：
2021-04
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影响因子：
--
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中科院分区：
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--
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微生理学系统（MPS），也称为器官芯片和组织芯片，是在各种物理和生化环境线索下用多种细胞类型构建的器官的小型化功能单元，作为药物发现和开发新范式的一部分，补充动物模型。仿生人类肝脏MPS已经从更简单的2D细胞模型、球状体和类器官发展而来，以满足日益增长的了解复杂和罕见疾病的患者特异性机制、对治疗性治疗的反应以及潜在治疗剂的吸收、分布、代谢、排泄和毒性的需求。跨学科技术的并行开发和应用，包括微流体装置，生物打印，工程基质材料，确定的生理和病理生理介质，患者来源的原代细胞和多能干细胞以及合成生物学工程细胞基因和功能，创造了生产患者特异性仿生MPS的潜力，用于详细的机理研究。预计具有已知基因型和完全成熟成人表型的患者源性MPS的开发和成熟的成功将导致精准医学的高级应用。在这篇综述中，我们研究了人类仿生肝MPS，旨在重现肝腺泡的结构和功能，以提高我们对疾病进展机制以及治疗候选药物和药物的吸收，分布，代谢，排泄和毒性的认识，并评估其作用机制及其在精准医学和临床前试验中的应用。
Microphysiology systems (MPS), also called organs-on-chips and tissue chips, are miniaturized functional units of organs constructed with multiple cell types under a variety of physical and biochemical environmental cues that complement animal models as part of a new paradigm of drug discovery and development. Biomimetic human liver MPS have evolved from simpler 2D cell models, spheroids and organoids to address the increasing need to understand patient-specific mechanisms of complex and rare diseases, the response to therapeutic treatments, and the absorption, distribution, metabolism, excretion and toxicity of potential therapeutics. The parallel development and application of transdisciplinary technologies, including microfluidic devices, bioprinting, engineered matrix materials, defined physiological and pathophysiological media, patient-derived primary cells, and pluripotent stem cells as well as synthetic biology to engineer cell genes and functions, have created the potential to produce patient-specific, biomimetic MPS for detailed mechanistic studies. It is projected that success in the development and maturation of patient-derived MPS with known genotypes and fully matured adult phenotypes will lead to advanced applications in precision medicine. In this Review, we examine human biomimetic liver MPS that are designed to recapitulate the liver acinus structure and functions to enhance our knowledge of the mechanisms of disease progression and of the absorption, distribution, metabolism, excretion and toxicity of therapeutic candidates and drugs as well as to evaluate their mechanisms of action and their application in precision medicine and preclinical trials.
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影响因子：
7.5
作者：
Bhushan A;Senutovitch N;Bale SS;McCarty WJ;Hegde M;Jindal R;Golberg I;Berk Usta O;Yarmush ML;Vernetti L;Gough A;Bakan A;Shun TY;DeBiasio R;Lansing Taylor D
通讯作者：
Lansing Taylor D
影响因子：
3.2
作者：
Bricks, Thibault;Paullier, Patrick;Leclerc, Eric
通讯作者：
Leclerc, Eric
影响因子：
6.1
作者：
Aref AR;Campisi M;Ivanova E;Portell A;Larios D;Piel BP;Mathur N;Zhou C;Coakley RV;Bartels A;Bowden M;Herbert Z;Hill S;Gilhooley S;Carter J;Cañadas I;Thai TC;Kitajima S;Chiono V;Paweletz CP;Barbie DA;Kamm RD;Jenkins RW
通讯作者：
Jenkins RW
DOI：
10.1513/pats.201001-016aw
发表时间：
2010-11-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Bouchecareilh, Marion;Conkright, Juliana J;Balch, William E
通讯作者：
Balch, William E
影响因子：
3.7
作者：
Beckwitt CH;Clark AM;Wheeler S;Taylor DL;Stolz DB;Griffith L;Wells A
通讯作者：
Wells A