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使用定义条件从人多能干细胞生成肾类器官。

Generating Kidney Organoids from Human Pluripotent Stem Cells Using Defined Conditions.

机构信息

Murdoch Children's Research Institute, Parkville, VIC, Australia.

Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia.

出版信息

Methods Mol Biol. 2020;2155:183-192. doi: 10.1007/978-1-0716-0655-1_15.

Abstract

The ultimate goal of regenerative medicine is to have access to an unlimited supply of specific cell types on demand, which can be used as effective therapies for a wide range of intractable disorders. With the availability of human pluripotent stem cells (hPSCs) and greatly improved protocols for their directed differentiation into specific cell types, including kidney, this prospect could soon become a reality. We have previously described the generation of kidney organoids from hPSCs. This chapter describes our latest differentiation protocol for generating kidney tissue, which uses a cost-effective and completely defined, xeno-free medium. As with our previous protocol, these complex, multicellular three-dimensional structures are composed of all anticipated kidney cell types including nephrons segmented into the glomerulus, proximal and distal tubule as well as an extensive endothelial network, and renal interstitium. As such, kidney organoids provide useful tools for understanding human development, disease modeling, drug screening/toxicology studies and tissue engineering applications, and may facilitate the development of transplantable hPSC-derived kidney tissue for regenerative medicine purposes in the future.

摘要

再生医学的最终目标是能够按需获得无限供应的特定细胞类型,这些细胞类型可作为广泛的难治性疾病的有效治疗方法。随着人类多能干细胞(hPSC)的出现和其定向分化为特定细胞类型(包括肾脏细胞)的方案的极大改进,这一前景可能很快成为现实。我们之前已经描述了从 hPSC 生成肾脏类器官。本章描述了我们最新的用于生成肾脏组织的分化方案,该方案使用具有成本效益且完全定义、无动物源的培养基。与我们之前的方案一样,这些复杂的、多细胞的三维结构由所有预期的肾脏细胞类型组成,包括肾小球、近端和远端肾小管以及广泛的内皮网络和肾间质。因此,肾脏类器官为理解人类发育、疾病建模、药物筛选/毒理学研究和组织工程应用提供了有用的工具,并且可能有助于未来为再生医学目的开发可移植的 hPSC 衍生的肾脏组织。

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