Symposium 3

Tomoji Mashimo
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引用次数: 1

Abstract

Humanized mouse in which human cells and tissues are engrafted and functioned in the mice is an important tool to mimic human physiology for biomedical and drug discovery researches. Although rodent models are generally used in preclinical studies investigating the efficacy and safety of novel drugs, they do not accurately evaluate the drug properties due to the species barrier. Non-human primates are valuable models for human diseases compared to rodents, but it is costly and requires a special breeding facility with expert for handling under strict ethical regulations. Severe combined immunodeficient NOG or NSG mice were developed independently in 2002 at CIEA or in 2005 at Jackson Laboratory. These mice exhibited multiple immunodeficiency lacking T, B and NK cells and functional defect of other innate immune cells. Therefore, the NOG or NSG mice have enabled high engraftment of primary human cells or tissues and to differentiate human T and B cells after human hematopoietic stem cell transplantation. However, human innate immune cells including NK cells, macrophages, granulocytes, mast cells, etc. do not fully differentiated in them. We aim to establish the next generation humanized mice in which various human cytokine genes are introduced to analyze human hematopoietic and immune systems and to develop human immune disease models. In the symposium, I provide an overview of the recent advances in humanized mouse technologies and applications for drug discovery in preclinical researches. The 66th Annual Meeting of Japanese Association for Laboratory Animal Science
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研讨会3
将人类细胞和组织移植并在小鼠体内发挥作用的人源化小鼠是生物医学和药物发现研究中模拟人类生理学的重要工具。尽管啮齿动物模型通常用于研究新药疗效和安全性的临床前研究,但由于物种屏障的原因,它们不能准确评估药物特性。与啮齿类动物相比,非人类灵长类动物是人类疾病的宝贵模型,但成本高昂,需要一个特殊的繁殖设施,由专家根据严格的道德规范进行处理。严重联合免疫缺陷NOG或NSG小鼠于2002年在CIEA或2005年在Jackson实验室独立开发。这些小鼠表现出缺乏T、B和NK细胞的多重免疫缺陷以及其他先天免疫细胞的功能缺陷。因此,NOG或NSG小鼠已经实现了原代人类细胞或组织的高植入,并在人类造血干细胞移植后分化人类T和B细胞。然而,包括NK细胞、巨噬细胞、粒细胞、肥大细胞等在内的人类先天免疫细胞在其中没有完全分化。我们的目标是建立下一代人源化小鼠,在其中引入各种人类细胞因子基因来分析人类造血和免疫系统,并开发人类免疫疾病模型。在研讨会上,我概述了人源化小鼠技术的最新进展以及药物发现在临床前研究中的应用。第66届日本实验动物科学协会年会
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