Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Michael Smith Building, Faculty of Biology Medicine and Health, University of Manchester, Oxford Road, Manchester, Northern Ireland M13 9PT, United Kingdom; Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Center, Manchester, Northern Ireland, United Kingdom.
J Pediatr Surg. 2022 Feb;57(2):172-177. doi: 10.1016/j.jpedsurg.2021.10.022. Epub 2021 Oct 29.
Severe kidney failure affects several million people worldwide. Among these are children born with abnormal renal tracts, and some carry mutations of genes active in renal tract development. Kidney transplants are in short supply, and long term dialysis does not obviate uraemia and its associated harmful effects. It has been envisaged that a combination of stem cell technology, developmental biology, and genetics will revolutionise our understanding of kidney disease and provide novel therapies for kidney failure. Here, we review progress towards making functional kidney tissues from human pluripotent stem cells. Organoids rich in immature glomeruli and tubules can be created in culture from pluripotent stem cells. Moreover, differentiation can be increased by implanting these cells into immunodeficient mice. Challenges remain to be overcome, however, before these tissues can be used for regenerative medicine therapies. Current limitations include the small size of an organoid, the lack of large blood vessels feeding it, and the lack of a urinary tract to plumb the kidney organoid. Pluripotent stem cell technology is also being used to create 'diseases in a dish' to understand the pathobiology underlying human renal tract malformations.
严重的肾衰竭影响了全球数百万人。其中包括出生时肾脏通道异常的儿童，以及一些携带肾脏通道发育相关基因变异的儿童。肾移植供不应求，长期透析并不能消除尿毒症及其相关的有害影响。人们设想，将干细胞技术、发育生物学和遗传学相结合，将彻底改变我们对肾脏疾病的认识，并为肾衰竭提供新的治疗方法。在这里，我们回顾了从人类多能干细胞中制造功能性肾脏组织的进展。在培养物中，可从多能干细胞中产生富含不成熟肾小球和肾小管的类器官。此外，通过将这些细胞植入免疫缺陷小鼠中，可以增加分化。然而，在这些组织可用于再生医学治疗之前，仍需克服一些挑战。目前的局限性包括类器官的体积小、缺乏为其提供营养的大血管以及缺乏排泄肾脏类器官的尿路。多能干细胞技术也被用于创建“疾病模型”，以了解人类肾脏通道畸形的病理生物学基础。
