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从多能干细胞生成人肾小球用于疾病建模和药物筛选。

Generating Human Glomeruli from Pluripotent Stem Cells for Disease Modelling and Drug Screening.

机构信息

Murdoch Children's Research Institute, Parkville, VIC, Australia.

UCB Pharma Ltd, Slough, UK.

出版信息

Methods Mol Biol. 2023;2664:55-68. doi: 10.1007/978-1-0716-3179-9_5.

Abstract

The functional unit of human kidney is the nephron. This structure is composed of a glomerulus, connected to a tubule that drains into a collecting duct. The cells which make up the glomerulus are critically important to the appropriate function of this specialised structure. Damage to glomerular cells, particularly the podocytes, is the primary cause of numerous kidney diseases. However, access to and the subsequent culture of human glomerular cells is limited. As such, the ability to generate human glomerular cell types from induced pluripotent stem cells (iPSCs) at scale has garnered great interest. Here, we describe a method to isolate, culture and study 3D human glomeruli from induced pluripotent stem cell (iPSC)-derived kidney organoids in vitro. These 3D glomeruli retain appropriate transcriptional profiles and can be generated from any individual. As isolated glomeruli, they have applicability for disease modelling and drug discovery.

摘要

人类肾脏的功能单位是肾单位。这个结构由一个肾小球组成,与一个肾小管相连,肾小管再排入集合管。构成肾小球的细胞对这个特殊结构的正常功能至关重要。肾小球细胞(特别是足细胞)的损伤是许多肾脏疾病的主要原因。然而,获取和随后培养人肾小球细胞是有限的。因此,能够从诱导多能干细胞(iPSCs)大规模生成人肾小球细胞类型引起了极大的兴趣。在这里,我们描述了一种从诱导多能干细胞(iPSC)衍生的肾类器官中分离、培养和研究 3D 人肾小球的方法。这些 3D 肾小球保留了适当的转录谱,并且可以从任何个体中产生。作为分离的肾小球,它们可用于疾病建模和药物发现。

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