Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Nat Rev Nephrol. 2019 Oct;15(10):613-624. doi: 10.1038/s41581-019-0176-x. Epub 2019 Aug 5.
Kidney organoids are regarded as important tools with which to study the development of the normal and diseased human kidney. Since the first reports of human pluripotent stem cell-derived kidney organoids 5 years ago, kidney organoids have been successfully used to model glomerular and tubular diseases. In parallel, advances in single-cell RNA sequencing have led to identification of a variety of cell types in the organoids, and have shown these to be similar to, but more immature than, human kidney cells in vivo. Protocols for the in vitro expansion of stem cell-derived nephron progenitor cells (NPCs), as well as those for the selective induction of specific lineages, especially glomerular podocytes, have also been reported. Although most current organoids are based on the induction of NPCs, an induction protocol for ureteric buds (collecting duct precursors) has also been developed, and approaches to generate more complex kidney structures may soon be possible. Maturation of organoids is a major challenge, and more detailed analysis of the developing kidney at a single cell level is needed. Eventually, organotypic kidney structures equipped with nephrons, collecting ducts, ureters, stroma and vascular flow are required to generate transplantable kidneys; such attempts are in progress.
肾类器官被认为是研究正常和病变人类肾脏发育的重要工具。自 5 年前首次报道人类多能干细胞衍生的肾类器官以来，肾类器官已成功用于模拟肾小球和肾小管疾病。与此同时，单细胞 RNA 测序的进展导致鉴定出类器官中的多种细胞类型，并表明这些细胞与体内的人类肾脏细胞相似，但更不成熟。体外扩增干细胞衍生的肾祖细胞（NPC）的方案，以及选择性诱导特定谱系的方案，特别是肾小球足细胞，也已被报道。尽管目前大多数类器官都是基于 NPC 的诱导，但也已经开发出输尿管芽（收集管前体）的诱导方案，并且生成更复杂的肾脏结构的方法可能很快就会成为可能。类器官的成熟是一个主要挑战，需要对单细胞水平的发育中的肾脏进行更详细的分析。最终，需要配备有肾单位、收集管、输尿管、基质和血管流的器官样结构来生成可移植的肾脏；正在进行此类尝试。
