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肾脏类器官的“3D”培养:肾单位发育、疾病建模和药物筛选的进展。

The "3Ds" of Growing Kidney Organoids: Advances in Nephron Development, Disease Modeling, and Drug Screening.

机构信息

Department of Biological Sciences, Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, Boler-Parseghian Center for Rare and Neglected Diseases, Warren Center for Drug Discovery, University of Notre Dame, Notre Dame, IN 46556, USA.

出版信息

Cells. 2023 Feb 8;12(4):549. doi: 10.3390/cells12040549.

DOI:10.3390/cells12040549
PMID:36831216
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9954122/
Abstract

A kidney organoid is a three-dimensional (3D) cellular aggregate grown from stem cells in vitro that undergoes self-organization, recapitulating aspects of normal renal development to produce nephron structures that resemble the native kidney organ. These miniature kidney-like structures can also be derived from primary patient cells and thus provide simplified context to observe how mutations in kidney-disease-associated genes affect organogenesis and physiological function. In the past several years, advances in kidney organoid technologies have achieved the formation of renal organoids with enhanced numbers of specialized cell types, less heterogeneity, and more architectural complexity. Microfluidic bioreactor culture devices, single-cell transcriptomics, and bioinformatic analyses have accelerated the development of more sophisticated renal organoids and tailored them to become increasingly amenable to high-throughput experimentation. However, many significant challenges remain in realizing the use of kidney organoids for renal replacement therapies. This review presents an overview of the renal organoid field and selected highlights of recent cutting-edge kidney organoid research with a focus on embryonic development, modeling renal disease, and personalized drug screening.

摘要

肾类器官是一种从体外干细胞中生长的三维(3D)细胞聚集体,经历自我组织,重现正常肾脏发育的某些方面,产生类似于天然肾脏器官的肾单位结构。这些微型肾样结构也可以从原代患者细胞中衍生而来,从而为观察肾脏疾病相关基因突变如何影响器官发生和生理功能提供简化的背景。在过去几年中,肾类器官技术的进步实现了具有更多特化细胞类型、更少异质性和更高结构复杂性的肾类器官的形成。微流控生物反应器培养装置、单细胞转录组学和生物信息学分析加速了更复杂的肾类器官的发展,并使它们更易于进行高通量实验。然而,在实现肾类器官用于肾脏替代疗法的应用方面,仍然存在许多重大挑战。本文综述了肾类器官领域的研究进展,并重点介绍了最近在胚胎发育、肾脏疾病建模和个性化药物筛选方面的前沿肾类器官研究的精选亮点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5c/9954122/fd5feee53a74/cells-12-00549-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5c/9954122/fb065fbfa154/cells-12-00549-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5c/9954122/fd5feee53a74/cells-12-00549-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5c/9954122/fb065fbfa154/cells-12-00549-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5c/9954122/fd5feee53a74/cells-12-00549-g002.jpg

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Adult human kidney organoids originate from CD24 cells and represent an advanced model for adult polycystic kidney disease.成人肾脏类器官来源于 CD24 细胞,代表了成人多囊肾病的先进模型。
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Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids.
利用类器官技术模拟风湿性和炎症性疾病中的自身免疫途径。
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Application of microphysiological systems to unravel the mechanisms of schistosomiasis egg extravasation.应用微生理系统揭示血吸虫虫卵外渗的机制。
Front Cell Infect Microbiol. 2025 Feb 18;15:1521265. doi: 10.3389/fcimb.2025.1521265. eCollection 2025.
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Recent advances in extracellular matrix manipulation for kidney organoid research.用于肾类器官研究的细胞外基质操控技术的最新进展
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Generative AI for Cell Type-Specific Fluorescence Image Generation of hPSC-derived Cardiac Organoid.用于生成人多能干细胞来源的心脏类器官特定细胞类型荧光图像的生成式人工智能。
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