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器官芯片在转化医学中的应用:疾病建模与再生医学。

Kidney organoids in translational medicine: Disease modeling and regenerative medicine.

机构信息

Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Department of Medicine, Harvard Medical School, Boston, Massachusetts.

出版信息

Dev Dyn. 2020 Jan;249(1):34-45. doi: 10.1002/dvdy.22. Epub 2019 Mar 26.

Abstract

The kidney is one of the most complex organs composed of multiple cell types, functioning to maintain homeostasis by means of the filtering of metabolic wastes, balancing of blood electrolytes, and adjustment of blood pressure. Recent advances in 3D culture technologies in vitro enabled the generation of "organoids" which mimic the structure and function of in vivo organs. Organoid technology has allowed for new insights into human organ development and human pathophysiology, with great potential for translational research. Increasing evidence shows that kidney organoids are a useful platform for disease modeling of genetic kidney diseases when derived from genetic patient iPSCs and/or CRISPR-mutated stem cells. Although single cell RNA-seq studies highlight the technical difficulties underlying kidney organoid generation reproducibility and variation in differentiation protocols, kidney organoids still hold great potential to understand kidney pathophysiology as applied to kidney injury and fibrosis. In this review, we summarize various studies of kidney organoids, disease modeling, genome-editing, and bioengineering, and additionally discuss the potential of and current challenges to kidney organoid research.

摘要

肾脏是由多种细胞类型组成的最复杂器官之一,通过过滤代谢废物、平衡血液电解质和调节血压来维持体内平衡。近年来,3D 体外培养技术的进步使得“类器官”的生成成为可能,这些类器官模拟了体内器官的结构和功能。类器官技术为人类器官发育和人类病理生理学提供了新的见解,具有转化研究的巨大潜力。越来越多的证据表明,当从遗传患者 iPSCs 和/或 CRISPR 突变干细胞中衍生时,肾类器官是遗传肾脏疾病疾病建模的有用平台。尽管单细胞 RNA-seq 研究强调了肾类器官生成重现性和分化方案变化的技术难题,但肾类器官仍然具有很大的潜力,可以应用于肾损伤和纤维化来理解肾脏病理生理学。在这篇综述中,我们总结了各种关于肾类器官、疾病建模、基因组编辑和生物工程的研究,并进一步讨论了肾类器官研究的潜力和当前挑战。

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本文引用的文献

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Nat Methods. 2019 Mar;16(3):255-262. doi: 10.1038/s41592-019-0325-y. Epub 2019 Feb 11.
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Evaluation of variability in human kidney organoids.人类肾类器官的变异性评估。
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