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基于人诱导多能干细胞的心肌和肝脏微生理组织模型用于药物开发。

Human induced pluripotent stem cell-based microphysiological tissue models of myocardium and liver for drug development.

出版信息

Stem Cell Res Ther. 2013;4 Suppl 1(Suppl 1):S14. doi: 10.1186/scrt375. Epub 2013 Dec 20.

Abstract

Drug discovery and development to date has relied on animal models, which are useful but are often expensive, slow, and fail to mimic human physiology. The discovery of human induced pluripotent stem (iPS) cells has led to the emergence of a new paradigm of drug screening using human and disease-specific organ-like cultures in a dish. Although classical static culture systems are useful for initial screening and toxicity testing, they lack the organization of differentiated iPS cells into microphysiological, organ-like structures deemed necessary for high-content analysis of candidate drugs. One promising approach to produce these organ-like structures is the use of advanced microfluidic systems, which can simulate tissue structure and function at a micron level, and can provide high-throughput testing of different compounds for therapeutic and diagnostic applications. Here, we provide a brief outline on the different approaches, which have been used to engineer in vitro tissue constructs of iPS cell-based myocardium and liver functions on chip. Combining these techniques with iPS cell biology has the potential of reducing the dependence on animal studies for drug toxicity and efficacy screening.

摘要

迄今为止,药物发现和开发一直依赖于动物模型,这些模型虽然有用,但通常昂贵、缓慢,并且无法模拟人体生理学。人类诱导多能干细胞 (iPS) 的发现导致了一种新的药物筛选范例的出现,即在培养皿中使用人类和疾病特异性类器官培养物进行筛选。尽管经典的静态培养系统对于初始筛选和毒性测试很有用,但它们缺乏将分化的 iPS 细胞组织成微生理、类器官结构的能力,而这种结构对于候选药物的高内涵分析是必要的。一种有前途的产生这些类器官结构的方法是使用先进的微流控系统,它可以在微米水平上模拟组织结构和功能,并可以为治疗和诊断应用提供高通量测试不同化合物的方法。在这里,我们简要概述了不同的方法,这些方法已被用于在芯片上工程化基于 iPS 细胞的心肌和肝脏功能的体外组织构建体。将这些技术与 iPS 细胞生物学相结合,有可能减少对动物研究的依赖,从而进行药物毒性和疗效筛选。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66a7/4029618/31147b364b1e/scrt375-1.jpg

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