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用于研究免疫介导性肾脏疾病的肾脏类器官系统:挑战与机遇。

Kidney organoid systems for studies of immune-mediated kidney diseases: challenges and opportunities.

机构信息

Research Department Virus Immunology, Leibniz-Institute for Experimental Virology, Hamburg, Germany.

III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

出版信息

Cell Tissue Res. 2021 Aug;385(2):457-473. doi: 10.1007/s00441-021-03499-4. Epub 2021 Jul 26.

Abstract

Acute and chronic kidney diseases are major contributors to morbidity and mortality in the global population. Many nephropathies are considered to be immune-mediated with dysregulated immune responses playing an important role in the pathogenesis. At present, targeted approaches for many kidney diseases are still lacking, as the underlying mechanisms remain insufficiently understood. With the recent development of organoids-a three-dimensional, multicellular culture system, which recapitulates important aspects of human tissues-new opportunities to investigate interactions between renal cells and immune cells in the pathogenesis of kidney diseases arise. To date, kidney organoid systems, which reflect the structure and closer resemble critical aspects of the organ, have been established. Here, we highlight the recent advances in the development of kidney organoid models, including pluripotent stem cell-derived kidney organoids and primary epithelial cell-based tubuloids. The employment and further required advances of current organoid models are discussed to investigate the role of the immune system in renal tissue development, regeneration, and inflammation to identify targets for the development of novel therapeutic approaches of immune-mediated kidney diseases.

摘要

急性和慢性肾脏疾病是全球人口发病率和死亡率的主要原因。许多肾脏病被认为是免疫介导的,免疫失调反应在发病机制中起着重要作用。目前,许多肾脏疾病的靶向治疗方法仍然缺乏,因为其潜在机制仍了解不足。随着器官类器官的最新发展——一种三维、多细胞培养系统,可重现人类组织的重要方面——为研究肾脏疾病发病机制中肾细胞和免疫细胞之间的相互作用提供了新的机会。迄今为止,已经建立了反映结构并更接近器官关键方面的肾脏类器官系统。在这里,我们重点介绍了肾脏类器官模型开发的最新进展,包括多能干细胞衍生的肾脏类器官和基于原代上皮细胞的肾小管类器官。讨论了当前类器官模型的应用和进一步需要的进展,以研究免疫系统在肾脏组织发育、再生和炎症中的作用,从而确定新型免疫介导的肾脏疾病治疗方法的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/747f/8523425/5f19f31d6a70/441_2021_3499_Fig1_HTML.jpg

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