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大型实验动物模型在测试糖尿病新治疗策略中的可行性。

Feasibility of large experimental animal models in testing novel therapeutic strategies for diabetes.

作者信息

Nagaya Masaki, Hasegawa Koki, Uchikura Ayuko, Nakano Kazuaki, Watanabe Masahito, Umeyama Kazuhiro, Matsunari Hitomi, Osafune Kenji, Kobayashi Eiji, Nakauchi Hiromitsu, Nagashima Hiroshi

机构信息

Meiji University International Institute for Bio-Resource Research, Meiji University, Kawasaki 214-8571, Kanagawa, Japan.

Laboratory of Medical Bioengineering, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Kanagawa, Japan.

出版信息

World J Diabetes. 2021 Apr 15;12(4):306-330. doi: 10.4239/wjd.v12.i4.306.

Abstract

Diabetes is among the top 10 causes of death in adults and caused approximately four million deaths worldwide in 2017. The incidence and prevalence of diabetes is predicted to increase. To alleviate this potentially severe situation, safer and more effective therapeutics are urgently required. Mice have long been the mainstay as preclinical models for basic research on diabetes, although they are not ideally suited for translating basic knowledge into clinical applications. To validate and optimize novel therapeutics for safe application in humans, an appropriate large animal model is needed. Large animals, especially pigs, are well suited for biomedical research and share many similarities with humans, including body size, anatomical features, physiology, and pathophysiology. Moreover, pigs already play an important role in translational studies, including clinical trials for xenotransplantation. Progress in genetic engineering over the past few decades has facilitated the development of transgenic animals, including porcine models of diabetes. This article discusses features that attest to the attractiveness of genetically modified porcine models of diabetes for testing novel treatment strategies using recent technical advances.

摘要

糖尿病是成年人十大死因之一,2017年全球约有400万人死于糖尿病。预计糖尿病的发病率和患病率将会上升。为缓解这一潜在的严峻形势,迫切需要更安全、更有效的治疗方法。长期以来,小鼠一直是糖尿病基础研究临床前模型的主要支柱,尽管它们并不完全适合将基础知识转化为临床应用。为验证和优化用于人类安全应用的新型疗法,需要合适的大型动物模型。大型动物,尤其是猪,非常适合生物医学研究,并且在体型、解剖特征、生理学和病理生理学等方面与人类有许多相似之处。此外,猪已经在转化研究中发挥重要作用,包括异种移植的临床试验。过去几十年基因工程的进展推动了转基因动物的发展,包括糖尿病猪模型。本文讨论了一些特性,这些特性证明了利用最新技术进展构建的转基因糖尿病猪模型在测试新型治疗策略方面具有吸引力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d90/8040081/8bd69bee5b74/WJD-12-306-g001.jpg

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