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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.

DOI:10.1007/978-1-0716-3179-9_5
PMID:37423982
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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Generating Human Glomeruli from Pluripotent Stem Cells for Disease Modelling and Drug Screening.从多能干细胞生成人肾小球用于疾病建模和药物筛选。
Methods Mol Biol. 2023;2664:55-68. doi: 10.1007/978-1-0716-3179-9_5.
2
3D organoid-derived human glomeruli for personalised podocyte disease modelling and drug screening.3D 类器官衍生的人肾小球用于个性化足细胞疾病建模和药物筛选。
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引用本文的文献

1
Podocytes in health and glomerular disease.健康与肾小球疾病中的足细胞。
Front Cell Dev Biol. 2025 Apr 24;13:1564847. doi: 10.3389/fcell.2025.1564847. eCollection 2025.

本文引用的文献

1
3D organoid-derived human glomeruli for personalised podocyte disease modelling and drug screening.3D 类器官衍生的人肾小球用于个性化足细胞疾病建模和药物筛选。
Nat Commun. 2018 Dec 4;9(1):5167. doi: 10.1038/s41467-018-07594-z.
2
Generation of kidney organoids from human pluripotent stem cells.从人类多能干细胞生成肾类器官。
Nat Protoc. 2016 Sep;11(9):1681-92. doi: 10.1038/nprot.2016.098. Epub 2016 Aug 18.
3
The glomerulus: the sphere of influence.肾小球:影响范围
Clin J Am Soc Nephrol. 2014 Aug 7;9(8):1461-9. doi: 10.2215/CJN.09400913. Epub 2014 May 29.
4
Podocyte mitosis - a catastrophe.足细胞有丝分裂——一场灾难。
Curr Mol Med. 2013 Jan;13(1):13-23. doi: 10.2174/1566524011307010013.
5
Role of the podocyte (and glomerular endothelium) in building the GBM.足细胞(和肾小球内皮细胞)在构建 GBM 中的作用。
Semin Nephrol. 2012 Jul;32(4):342-9. doi: 10.1016/j.semnephrol.2012.06.005.
6
Human nephron number: implications for health and disease.人类肾单位数量:对健康和疾病的影响。
Pediatr Nephrol. 2011 Sep;26(9):1529-33. doi: 10.1007/s00467-011-1843-8. Epub 2011 May 22.
7
Culture methods of glomerular podocytes.肾小球足细胞的培养方法。
Kidney Blood Press Res. 2007;30(3):162-74. doi: 10.1159/000102520.
8
The spectrum of podocytopathies: a unifying view of glomerular diseases.足细胞病谱:肾小球疾病的统一观点
Kidney Int. 2007 Jun;71(12):1205-14. doi: 10.1038/sj.ki.5002222. Epub 2007 Apr 4.