Murdoch Children's Research Institute, Flemington Rd, Parkville, VIC, Australia; Department of Paediatrics, The University of Melbourne, VIC, Australia; Department of Anatomy and Neuroscience, The University of Melbourne, VIC, Australia.
Dev Biol. 2021 Jun;474:22-36. doi: 10.1016/j.ydbio.2020.12.009. Epub 2021 Jan 7.
There is no doubt that the development of transplantable synthetic kidneys could improve the outcome for the many millions of people worldwide suffering from chronic kidney disease. Substantial progress has been made in the last 6 years in the generation of kidney tissue from stem cells. However, the limited scale, incomplete cellular complexity and functional immaturity of such structures suggests we are some way from this goal. While developmental biology has successfully guided advances to date, these human kidney models are limited in their capacity for ongoing nephrogenesis and lack corticomedullary definition, a unified vasculature and a coordinated exit path for urinary filtrate. This review will reassess our developmental understanding of how the mammalian embryo manages to create kidneys, how this has informed our progress to date and how both engineering and developmental biology can continue to guide us towards a synthetic kidney.
毫无疑问,可移植的合成肾脏的发展可以改善全球数以百万计的慢性肾脏疾病患者的预后。在过去的 6 年中,干细胞生成肾脏组织方面取得了重大进展。然而,这些结构的规模有限、细胞复杂性不完整以及功能不成熟表明,我们还有很长的路要走。尽管发育生物学成功地指导了迄今为止的进展,但这些人类肾脏模型在持续肾发生的能力上受到限制,并且缺乏皮质-髓质定义、统一的脉管系统以及尿液滤出物的协调出口途径。这篇综述将重新评估我们对哺乳动物胚胎如何设法创建肾脏的发育理解,以及这如何告知我们迄今为止的进展,以及工程学和发育生物学如何继续指导我们走向合成肾脏。