Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Department of Nephrology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Dev Growth Differ. 2021 Feb;63(2):166-177. doi: 10.1111/dgd.12714. Epub 2021 Mar 21.
Kidney organoids generated from human pluripotent stem cells (hPSCs) have drastically changed the field of stem cell research on human kidneys within a few years. They are self-organizing multicellular structures that contain nephron components such as glomeruli and renal tubules in most cases, but hPSC-derived ureteric buds, the progenitors of collecting ducts and ureters, can also form three-dimensional organoids. Today's challenges facing human kidney organoids are further maturation and anatomical integrity in order to achieve a complete model of the developing kidneys and ultimately a complete adult organ. Since chronic kidney disease (CKD) and impaired kidney function are an increasing burden on public health worldwide, there is an urgent need to develop effective treatments for various renal conditions. In this regard, hPSC-derived kidney organoids may impact medicine by providing new translational approaches. The unique ability of kidney organoids derived from disease-specific hPSCs to reproduce human diseases caused by genetic alterations may help provide the next generation of kidney disease models. Recent advances in the field of kidney organoid research have been generally accompanied by progress in developmental biology and other technological breakthroughs. In this review, we consider the current trends in kidney organoid technology, especially focusing on the relationship to the study of human kidney development, and discuss the remaining hurdles and prospects in regenerating human kidney structures beyond organoids.
由人类多能干细胞 (hPSC) 生成的肾脏类器官在短短几年内彻底改变了人类肾脏干细胞研究领域。它们是自我组织的多细胞结构,在大多数情况下包含肾小球和肾小管等肾单位成分,但 hPSC 衍生的输尿管芽,即收集管和输尿管的祖细胞,也可以形成三维类器官。目前,人类肾脏类器官面临的挑战是进一步成熟和保持解剖完整性,以实现发育中肾脏的完整模型,最终实现完整的成人器官。由于慢性肾脏病 (CKD) 和肾功能受损给全球公共卫生带来的负担日益加重,迫切需要开发针对各种肾脏疾病的有效治疗方法。在这方面,hPSC 衍生的肾脏类器官可能通过提供新的转化方法对医学产生影响。源自特定于疾病的 hPSC 的肾脏类器官具有再现由遗传改变引起的人类疾病的独特能力,这可能有助于提供下一代肾脏疾病模型。近年来,肾脏类器官研究领域的进展总体上伴随着发育生物学和其他技术突破的进展。在这篇综述中,我们考虑了肾脏类器官技术的当前趋势,特别是侧重于与人类肾脏发育研究的关系,并讨论了在超越类器官再生人类肾脏结构方面仍然存在的障碍和前景。