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Human reconstructed kidney models
In Vitro Cellular & Developmental Biology - Animal ( IF 1.5 ) Pub Date : 2021-02-16 , DOI: 10.1007/s11626-021-00548-8
Seiji Kishi 1 , Takuya Matsumoto 2 , Takaharu Ichimura 3 , Craig R Brooks 4
Affiliation  

The human kidney, which consists of up to 2 million nephrons, is critical for blood filtration, electrolyte balance, pH regulation, and fluid balance in the body. Animal experiments, particularly mice and rats, combined with advances in genetically modified technology have been the primary mechanism to study kidney injury in recent years. Mouse or rat kidneys, however, differ substantially from human kidneys at the anatomical, histological, and molecular levels. These differences combined with increased regulatory hurdles and shifting attitudes towards animal testing by non-specialists have led scientists to develop new and more relevant models of kidney injury. Although in vitro tissue culture studies are a valuable tool to study kidney injury and have yielded a great deal of insight, they are not a perfect model. Perhaps, the biggest limitation of tissue culture is that it cannot replicate the complex architecture, consisting of multiple cell types, of the kidney, and the interplay between these cells. Recent studies have found that pluripotent stem cells (PSCs), which are capable of differentiation into any cell type, can be used to generate kidney organoids. Organoids recapitulate the multicellular relationships and microenvironments of complex organs like kidney. Kidney organoids have been used to successfully model nephrotoxin-induced tubular and glomerular disease as well as complex diseases such as chronic kidney disease (CKD), which involves multiple cell types. In combination with genetic engineering techniques, such as CRISPR-Cas9, genetic diseases of the kidney can be reproduced in organoids. Thus, organoid models have the potential to predict drug toxicity and enhance drug discovery for human disease more accurately than animal models.



中文翻译:

人体重建肾脏模型

人体肾脏由多达 200 万个肾单位组成,对体内的血液过滤、电解质平衡、pH 调节和体液平衡至关重要。动物实验,特别是小鼠和大鼠,结合转基因技术的进步,是近年来研究肾损伤的主要机制。然而,小鼠或大鼠肾脏在解剖学、组织学和分子水平上与人类肾脏有很大不同。这些差异加上监管障碍的增加以及非专家对动物试验的态度转变,导致科学家们开发出新的、更相关的肾损伤模型。尽管体外组织培养研究是研究肾损伤的宝贵工具,并产生了很多见解,但它们并不是一个完美的模型。也许,组织培养的最大限制是它无法复制由多种细胞类型组成的肾脏的复杂结构以及这些细胞之间的相互作用。最近的研究发现,能够分化成任何细胞类型的多能干细胞 (PSC) 可用于生成肾脏类器官。类器官概括了肾脏等复杂器官的多细胞关系和微环境。肾脏类器官已被用于成功模拟肾毒素引起的肾小管和肾小球疾病以及复杂疾病,例如涉及多种细胞类型的慢性肾病 (CKD)。结合基因工程技术,例如 CRISPR-Cas9,肾脏的遗传疾病可以在类器官中复制。因此,

更新日期:2021-02-17
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