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基于诱导多能干细胞的微生理系统在药物研发与测试中的应用

Utility of Induced Pluripotent Stem Cell-Based Microphysiological Systems for Drug Development and Testing.

作者信息

van Noort Danny, Mandenius Carl-Fredrik

机构信息

Division of Biophysics and Bioengineering, Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.

出版信息

Methods Mol Biol. 2025;2924:165-187. doi: 10.1007/978-1-0716-4530-7_12.

DOI:10.1007/978-1-0716-4530-7_12
PMID:40307642
Abstract

Microphysiological systems (MPS), i.e., miniaturized mimics of active biological systems, are considered resourceful tools for facilitating drug development. It presupposes that a microphysiological system can respond as organs and tissues in the human body to new drug candidates and that relevant cellular response can be monitored. If, or when, this is possible, microphysiological systems have the potential to support and accelerate the development and testing of new drug candidates.So far, the focus has been more on the design and fabrication of the microarchitecture of the MPS to recreate their cellular counterparts as closely and realistically as possible. Commercial MPS devices have been developed that focus on advanced technological design solutions, sometimes more than their actual biological functionality.This chapter discusses in brief terms the prerequisites for the design and construction of MPS devices in relation to their utility for drug development and testing in a more holistic manner. The use of induced pluripotent cells as a prime source for mimicking the in vivo conditions of diseased conditions is mainly considered. Existing limitations and needs are highlighted in relation to the space for improvements, based on recently published results.

摘要

微生理系统(MPS),即活性生物系统的小型化模拟物,被认为是促进药物开发的有用工具。这预先假定微生理系统能够像人体中的器官和组织一样对新的候选药物作出反应,并且能够监测相关的细胞反应。如果或者当这成为可能时,微生理系统有潜力支持并加速新候选药物的开发和测试。到目前为止,重点更多地放在了MPS微结构的设计和制造上,以便尽可能紧密和逼真地重现其细胞对应物。已经开发出了商业化的MPS设备,这些设备有时更侧重于先进的技术设计解决方案,而非其实际的生物学功能。本章简要讨论了MPS设备的设计和构建的先决条件,以及它们在药物开发和测试中以更全面方式发挥作用的情况。主要考虑了使用诱导多能细胞作为模拟疾病体内状况的主要来源。基于最近发表的结果,针对改进空间突出了现有局限性和需求。

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本文引用的文献

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Contractile and Genetic Characterization of Cardiac Constructs Engineered from Human Induced Pluripotent Stem Cells: Modeling of Tuberous Sclerosis Complex and the Effects of Rapamycin.源自人类诱导多能干细胞的心脏构建体的收缩和遗传特征:结节性硬化症复合体的建模及雷帕霉素的作用
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人工智能驱动的类器官:构建、分析与应用。
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