Kidney micro-organoids in suspension culture as a scalable source of human pluripotent stem cell-derived kidney cells

Kidney micro-organoids in suspension culture as a scalable source of human pluripotent stem cell-derived kidney cells
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DOI:
10.1242/dev.172361
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发表时间:
2019-03-01
期刊:
影响因子:
4.6
通讯作者:
Little, Melissa H.
Little, Melissa H.
中科院分区:
生物学2区
文献类型:
--
作者:
Kumar, Santhosh, V;Er, Pei X.;Little, Melissa H.

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肾脏类器官在疾病建模、药物筛选和再生医学方面具有潜在的用途。然而,需要新的具有成本效益的技术来实现体外肾细胞类型的规模化生产。我们在这里描述了一种改良的悬浮培养方法,用于从人多能干细胞产生肾脏微类器官。分化条件的优化允许形成微型类器官,每个类器官含有6至10个被内皮和基质群体包围的肾单位。单细胞转录谱分析证实了所有预期肾细胞类型的存在和转录等效性,与先前的类器官培养方法一致。与静态培养相比,这种悬浮培养微类器官方法导致最终细胞产量增加三至四倍,从而代表了用于各种生物学应用的肾细胞生产的经济方法。
Kidney organoids have potential uses in disease modelling, drug screening and regenerative medicine. However, novel cost-effective techniques are needed to enable scaled-up production of kidney cell types in vitro. We describe here a modified suspension culture method for the generation of kidney micro-organoids from human pluripotent stem cells. Optimisation of differentiation conditions allowed the formation of micro-organoids, each containing six to ten nephrons that were surrounded by endothelial and stromal populations. Single cell transcriptional profiling confirmed the presence and transcriptional equivalence of all anticipated renal cell types consistent with a previous organoid culture method. This suspension culture micro-organoid methodology resulted in a three- to fourfold increase in final cell yield compared with static culture, thereby representing an economical approach to the production of kidney cells for various biological applications.