Studying Kidney Diseases Using Organoid Models.
Studying Kidney Diseases Using Organoid Models.
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DOI：
10.3389/fcell.2022.845401
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发表时间：
2022
影响因子：
5.5
通讯作者：
Xia Y
中科院分区：
文献类型：
--
作者：
Liu M;Cardilla A;Ngeow J;Gong X;Xia Y
由于全球糖尿病和心血管疾病的增加，慢性肾脏病（CKD）的患病率在过去几十年中迅速增加。透析极大地损害了患者的生活质量，同时无法满足可移植肾的需求，这凸显了开发新的治疗方法来阻止或逆转 CKD 进展的必要性。我们对肾脏疾病的了解主要来源于使用动物模型和细胞培养的研究。虽然跨物种差异使得将动物模型的研究结果完全转化为临床实践具有挑战性，但原代患者细胞在体外培养过程中很快就会失去原始表型。在过去的十年中，通过将干细胞暴露于模拟特定器官或组织发育所需信号线索的培养条件，在生成 3 维 (3D) 微型器官（类器官）方面取得了显着的成就。 3D 肾脏类器官已成功从不同类型的源细胞中生成，包括人类多能干细胞 (hPSC)、成人/胎儿肾组织和肾癌活检。除了基因编辑工具之外，hPSC 衍生的肾脏类器官也被用来模拟遗传性肾脏疾病。相比之下，成人肾源性小管和肾癌源性肿瘤仍处于婴儿期。在这里，我们首先总结了目前可用的肾脏类器官模型。接下来，我们讨论使用类器官模型进行肾脏疾病建模的最新进展。最后，我们考虑了阻碍肾脏类器官在疾病建模和药物评价中应用的主要挑战，并提出了前瞻性的解决方案。
The prevalence of chronic kidney disease (CKD) is rapidly increasing over the last few decades, owing to the global increase in diabetes, and cardiovascular diseases. Dialysis greatly compromises the life quality of patients, while demand for transplantable kidney cannot be met, underscoring the need to develop novel therapeutic approaches to stop or reverse CKD progression. Our understanding of kidney disease is primarily derived from studies using animal models and cell culture. While cross-species differences made it challenging to fully translate findings from animal models into clinical practice, primary patient cells quickly lose the original phenotypes during in vitro culture. Over the last decade, remarkable achievements have been made for generating 3-dimensional (3D) miniature organs (organoids) by exposing stem cells to culture conditions that mimic the signaling cues required for the development of a particular organ or tissue. 3D kidney organoids have been successfully generated from different types of source cells, including human pluripotent stem cells (hPSCs), adult/fetal renal tissues, and kidney cancer biopsy. Alongside gene editing tools, hPSC-derived kidney organoids are being harnessed to model genetic kidney diseases. In comparison, adult kidney-derived tubuloids and kidney cancer-derived tumoroids are still in their infancy. Herein, we first summarize the currently available kidney organoid models. Next, we discuss recent advances in kidney disease modelling using organoid models. Finally, we consider the major challenges that have hindered the application of kidney organoids in disease modelling and drug evaluation and propose prospective solutions.
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DOI：
10.1084/jem.194.1.13
发表时间：
2001-07-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Doyonnas R;Kershaw DB;Duhme C;Merkens H;Chelliah S;Graf T;McNagny KM
通讯作者：
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影响因子：
23.9
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通讯作者：
Freedman BS
影响因子：
16.6
作者：
Calandrini, Camilla;Schutgens, Frans;Drost, Jarno
通讯作者：
Drost, Jarno
影响因子：
1.5
作者：
Cristofori, Patrizia;Zanetti, Edoardo;Trevisan, Andrea
通讯作者：
Trevisan, Andrea
DOI：
10.1038/s41573-021-00242-0
发表时间：
2021-10
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Daehn IS;Duffield JS
通讯作者：
Duffield JS