Steichen Clara, Giraud Sébastien, Hauet Thierry
Inserm U1082 - IRTOMIT (Ischémie reperfusion en transplantation d'organes mécanismes et innovations thérapeutiques), Poitiers, F-86000, France - Université de Poitiers, Faculté de médecine et de pharmacie, Poitiers, F-86000, France.
Inserm U1082 - IRTOMIT (Ischémie reperfusion en transplantation d'organes mécanismes et innovations thérapeutiques), Poitiers, F-86000, France - CHU de Poitiers, service de biochimie, Poitiers, F-86000, France.
Med Sci (Paris). 2019 May;35(5):470-477. doi: 10.1051/medsci/2019090. Epub 2019 May 22.
This review focus on kidney organoids derived from pluripotent stem cells, which become a real alternative to the use of in vitro cellular models or in vivo animals models. 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 kidney organoids that are highly complex and organized structures, composed of various renal cell types. These mini-organs are endowed with major applications: the possibility to control iPSC genome (by selecting patients with specific disease or by genome editing) allows the generation of kidney organoïds which recapitulate important physiopathological mechanisms such as cyste formation in renal polycystic disease. Kidney organoids can also be used in high-throughput screening to fasten the screening of nephrotoxic/therapeutic compounds. Finally, kidney organoids have a huge interest in the context of tissue repair, which remains for now a challenging goal linked with technological barriers that need still to be overcome.
本综述聚焦于源自多能干细胞的肾脏类器官,其已成为体外细胞模型或体内动物模型使用的一种切实可行的替代方案。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肾脏类器官,即由各种肾细胞类型组成的高度复杂且有组织的结构。这些微型器官具有重要应用:通过控制诱导多能干细胞基因组(通过选择患有特定疾病的患者或进行基因组编辑),能够生成可重现重要生理病理机制(如肾多囊病中囊肿形成)的肾脏类器官。肾脏类器官还可用于高通量筛选,以加速对肾毒性/治疗性化合物的筛选。最后,肾脏类器官在组织修复方面具有巨大潜力,目前这仍是一个具有挑战性的目标,与仍需克服的技术障碍相关。