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结合肾类器官与基因组编辑技术以更好地理解肾脏疾病的生理病理机制:现状

Combining Kidney Organoids and Genome Editing Technologies for a Better Understanding of Physiopathological Mechanisms of Renal Diseases: State of the Art.

作者信息

Steichen Clara, Giraud Sébastien, Hauet Thierry

机构信息

INSERM U1082-IRTOMIT, Poitiers, France.

Université de Poitiers, Faculté de Médecine et de Pharmacie, Poitiers, France.

出版信息

Front Med (Lausanne). 2020 Feb 4;7:10. doi: 10.3389/fmed.2020.00010. eCollection 2020.

Abstract

Kidney organoids derived from pluripotent stem cells became a real alternative to the use of cellular models or animal models. Indeed, the comprehension of the key steps involved during kidney embryonic development led to the establishment of protocols enabling the differentiation of pluripotent stem cells into highly complex and organized structures, composed of various renal cell types. These organoids are linked with one major application based on iPSC technology advantage: the possibility to control iPSC genome, by selecting patients with specific disease or by genome editing tools such as CRISPR/Cas9 system. This allows the generation of kidney organoïds which recapitulate important physiopathological mechanisms such as cyst formation in renal polycystic disease for example. This review will focus on studies combining these both cutting edge technologies i.e., kidney organoid differentiation and genome editing and will describe what are the main advances performed in the comprehension of physiopathological mechanisms of renal diseases, as well as discuss remaining technical barriers and perspectives in the field.

摘要

源自多能干细胞的肾类器官成为了细胞模型或动物模型应用的真正替代方案。事实上,对肾脏胚胎发育过程中关键步骤的理解促使了相关方案的建立,这些方案能够使多能干细胞分化为高度复杂且有组织的结构,该结构由各种肾细胞类型组成。这些类器官与基于诱导多能干细胞(iPSC)技术优势的一项主要应用相关联:通过选择患有特定疾病的患者或借助CRISPR/Cas9系统等基因组编辑工具来控制iPSC基因组的可能性。这使得能够生成可重现重要生理病理机制的肾类器官,例如肾多囊病中的囊肿形成。本综述将聚焦于结合这两种前沿技术(即肾类器官分化和基因组编辑)的研究,并描述在理解肾脏疾病生理病理机制方面取得的主要进展,同时讨论该领域尚存的技术障碍和前景。

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