[利用iPS细胞和计算机模型发现药物]。

Yuya Fujiwara, Yoshinori Yoshida
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引用次数: 0

摘要

人类诱导多能干细胞衍生的心肌细胞(hiPSC-CMs)可以概括人类心肌细胞的特性,并在体外表现出疾病表型,这可归因于其健康或患者特异性的遗传背景。因此,hiPSC-CMs是开发心血管疾病治疗剂的重要工具,使用hiPSC-CMs的再生医学有望成为心脏移植的替代疗法。此外,类器官模型的发展已经取得了进展,可以在体外复制心脏组织的复杂结构,从而有效地促进药物的发现。另一方面,目前利用hiPSC-CMs推进药物发现的方法面临局限性,包括难以量化细胞结构等特征,以及难以预测临床实践中候选药物的风险和疗效。在再生医学领域,面临的挑战包括人体移植细胞的质量控制和安全性验证。利用hiPSC-CMs在药物发现领域开发了包括人工智能(AI)和仿真在内的计算机模型。这些进步包括通过人工智能进行表型评分和通过模拟进行风险预测。本文以已发表的报告为基础,概述了利用hiPSC-CMs和硅模型进行药物发现的现状和挑战。
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[Drug discovery using iPS cells and in silico model].

Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) can recapitulate the properties of human cardiomyocyte and exhibit disease phenotypes in vitro, attributable to their healthy- or patient-specific genetic backgrounds. Therefore, hiPSC-CMs are a crucial tool for developing therapeutic agents for cardiovascular diseases, and regenerative medicine using hiPSC-CMs is expected to be an alternative therapy to heart transplantation. Moreover, the development of organoid models has been advanced to replicate the complex structure of heart tissue in vitro, thereby effectively facilitating drug discovery. On the other hand, current methods for advancing drug discovery using hiPSC-CMs face limitations, including the difficulty of quantifying characteristics such as cell structure and predicting the risk and efficacy of candidate drug in clinical practice. In the field of regenerative medicine, challenges include quality control and the verification of safety of transplanted cells in human. In silico model, including artificial intelligence (AI) and simulation, have been developed in the field of drug discovery using hiPSC-CMs. These advancements encompass phenotype scoring via AI and risk prediction through simulations. This review outlines the current status and challenges of drug discovery using hiPSC-CMs and in silico model, based on the published reports.

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来源期刊
Folia Pharmacologica Japonica
Folia Pharmacologica Japonica Pharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
0.40
自引率
0.00%
发文量
132
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