Multiorgan Microphysiological Systems for Drug Development: Strategies, Advances, and Challenges.
Multiorgan Microphysiological Systems for Drug Development: Strategies, Advances, and Challenges.
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DOI：
10.1002/adhm.201701000
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发表时间：
2018-01
影响因子：
10
通讯作者：
Shuler ML
中科院分区：
文献类型：
--
作者：
Wang YI;Carmona C;Hickman JJ;Shuler ML
用于临床前药物筛选的传统细胞培养和动物模型导致临床试验中候选药物的高损耗率，因为它们对人体反应的预测能力较低。利用人体细胞构建具有生理相关器官-器官相互作用的人体体外仿生学的替代模型具有作为“人体替代品”的巨大潜力，并提供更准确的药物对人体的影响预测。本文综述了基于组织工程的人体细胞微尺度多器官模型或多器官微生理系统药物测试的研究进展。讨论了从传统模型到宏观和微观尺度多器官系统的演变，以及最近全球多器官微生理系统研究的基本原理。目前在整合细胞培养和芯片上分析技术的进展，以及这些多器官微系统的概念验证应用进行了讨论。讨论了该领域面临的主要挑战，如可重复性和生理相关性，并比较了解决这些挑战的各种系统的优缺点。总结了目前多器官微生理系统的发展阶段和该领域的新趋势。多器官微生理（MOM）系统是体外微尺度人体细胞培养模拟物（人体芯片）。组织工程单器官模型相互关联，以再现复杂的多器官相互作用。这种人体仿生学可以潜在地作为“人体替代品”来模拟人体对药物的反应，提供药代动力学和药效学信息。
Traditional cell culture and animal models utilized for preclinical drug screening have led to high attrition rates of drug candidates in clinical trials due to their low predictive power for human response. Alternative models using human cells to build in vitro biomimetics of the human body with physiologically relevant organ-organ interactions hold great potential to act as “human surrogates” and provide more accurate prediction of drug effects in humans. This review is a comprehensive investigation into the development of tissue-engineered human cell-based microscale multi-organ models, or multi-organ microphysiological systems for drug testing. The evolution from traditional models to macro- and microscale multi-organ systems are discussed in regards to the rationale for recent global efforts in multi-organ microphysiological systems. Current advances in integrating cell culture and on-chip analytical technologies, as well as proof-of-concept applications for these multi-organ microsystems are discussed. Major challenges for the field, such as reproducibility and physiological relevance, are discussed with comparisons of the strengths and weaknesses of various systems to solve these challenges. Conclusions focus on the current development stage of multi-organ microphysiological systems and new trends in the field. Multi-organ microphysiological (MOM) systems are in vitro microscale cell culture analog of the human body (Body-on-a-chip). Tissue engineered single organ models are interconnected to reproduce complex multi-organ interactions. Such biomimetics of the human body can potentially serve as “human surrogates” to simulate human responses to drugs, providing pharmacokinetic and pharmacodynamic information.
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影响因子：
7.3
作者：
Benson K;Cramer S;Galla HJ
通讯作者：
Galla HJ
DOI：
10.1113/expphysiol.1981.sp002529
发表时间：
1981-01-01
影响因子：
--
作者：
BARKER, G;SIMMONS, NL
通讯作者：
SIMMONS, NL
DOI：
10.1602/neurorx.2.4.554
发表时间：
2005-10-01
期刊：
NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics
影响因子：
--
作者：
Alavijeh, Mohammad S;Chishty, Mansoor;Palmer, Alan M
通讯作者：
Palmer, Alan M
影响因子：
3.2
作者：
Bricks, Thibault;Paullier, Patrick;Leclerc, Eric
通讯作者：
Leclerc, Eric
影响因子：
1.7
作者：
Bianconi, Eva;Piovesan, Allison;Canaider, Silvia
通讯作者：
Canaider, Silvia