Critical Considerations for the Design of Multi-Organ Microphysiological Systems (MPS).
Critical Considerations for the Design of Multi-Organ Microphysiological Systems (MPS).
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DOI：
10.3389/fcell.2021.721338
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发表时间：
2021
影响因子：
5.5
通讯作者：
Esch MB
中科院分区：
文献类型：
--
作者：
Malik M;Yang Y;Fathi P;Mahler GJ;Esch MB
识别和批准用于患者的新药需要广泛的临床前研究和临床试验。临床前研究依赖于体外实验和人类疾病的动物模型。从动物模型到人类的药物毒性和疗效估计的可转移性正受到质疑。随后的临床研究往往显示，与动物模型相比，人类的疗效低于预期，药物毒性更高。微生理系统(MPS)，有时被称为器官或人类芯片模型，为用于药物毒性筛选的动物模型提供了一种潜在的替代方案。该综述讨论了可用于疾病模型和测试候选药物的有效性和安全性的多器官MPS。将体内环境转换为体外系统需要生理上相关的器官缩放、血管大小和适当的流速。即使这些参数的微小变化也会改变用MPS进行的实验的结果。随着许多MPS设备的开发，我们已经概述了一些已建立的MPS设备设计标准，并描述了验证设备的技术。生理上逼真的人体模拟可以帮助确定具有更高预测能力的新候选药物的剂量反应和毒性效应。
Identification and approval of new drugs for use in patients requires extensive preclinical studies and clinical trials. Preclinical studies rely on in vitro experiments and animal models of human diseases. The transferability of drug toxicity and efficacy estimates to humans from animal models is being called into question. Subsequent clinical studies often reveal lower than expected efficacy and higher drug toxicity in humans than that seen in animal models. Microphysiological systems (MPS), sometimes called organ or human-on-chip models, present a potential alternative to animal-based models used for drug toxicity screening. This review discusses multi-organ MPS that can be used to model diseases and test the efficacy and safety of drug candidates. The translation of an in vivo environment to an in vitro system requires physiologically relevant organ scaling, vascular dimensions, and appropriate flow rates. Even small changes in those parameters can alter the outcome of experiments conducted with MPS. With many MPS devices being developed, we have outlined some established standards for designing MPS devices and described techniques to validate the devices. A physiologically realistic mimic of the human body can help determine the dose response and toxicity effects of a new drug candidate with higher predictive power.
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影响因子：
7.4
作者：
Douville, Nicholas J.;Tung, Yi-Chung;Li, Ran;Wang, Jack D.;El-Sayed, Mohamed E. H.;Takayama, Shuichi
通讯作者：
Takayama, Shuichi
影响因子：
4.6
作者：
Edington CD;Chen WLK;Geishecker E;Kassis T;Soenksen LR;Bhushan BM;Freake D;Kirschner J;Maass C;Tsamandouras N;Valdez J;Cook CD;Parent T;Snyder S;Yu J;Suter E;Shockley M;Velazquez J;Velazquez JJ;Stockdale L;Papps JP;Lee I;Vann N;Gamboa M;LaBarge ME;Zhong Z;Wang X;Boyer LA;Lauffenburger DA;Carrier RL;Communal C;Tannenbaum SR;Stokes CL;Hughes DJ;Rohatgi G;Trumper DL;Cirit M;Griffith LG
通讯作者：
Griffith LG
影响因子：
6.1
作者：
Esch MB;Prot JM;Wang YI;Miller P;Llamas-Vidales JR;Naughton BA;Applegate DR;Shuler ML
通讯作者：
Shuler ML
影响因子：
5.6
作者：
Adiwidjaja, Jeffry;Boddy, Alan V.;McLachlan, Andrew J.
通讯作者：
McLachlan, Andrew J.
影响因子：
6.7
作者：
BARGETZI, MJ;AOYAMA, T;MEYER, UA
通讯作者：
MEYER, UA