Hasegawa Sho, Tanaka Tetsuhiro, Nangaku Masaomi
Division of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
F1000Res. 2019 Feb 25;8. doi: 10.12688/f1000research.17127.1. eCollection 2019.
Regeneration of a functional kidney from pluripotent stem cells (PSCs) is challenging because of its complex structure. Kidneys are derived from embryonic metanephros, which are composed of three progenitor cells: nephron progenitors, ureteric bud, and stromal progenitors. Nephron progenitors and ureteric bud have been induced successfully from PSCs as a result of the understanding of their detailed developmental process through cell-lineage tracing analysis. Moreover, these induced progenitors can be used to reconstruct the three-dimensional (3D) structure of kidneys , including glomeruli with podocytes, renal tubules, and the branching ureters. Induction of the remaining renal progenitors (that is, stromal progenitors from PSCs and the further maturation of reconstructed kidneys) needs to be studied extensively to regenerate functional and sophisticated kidneys from PSCs. In addition to the proper induction of renal progenitors, new bioengineering methods such as decellularization and 3D bioprinting and the recent advancements in the regeneration of kidneys in other species are promising leads for regenerating the complex spatial arrangement of kidneys, including the vascular network and urinary excretion pathway in humans.
由于肾脏结构复杂，从多能干细胞（PSC）再生出功能性肾脏具有挑战性。肾脏起源于胚胎后肾，由三种祖细胞组成：肾单位祖细胞、输尿管芽和基质祖细胞。通过细胞谱系追踪分析对肾单位祖细胞和输尿管芽详细发育过程的了解，已成功从PSC诱导出这些细胞。此外，这些诱导的祖细胞可用于重建肾脏的三维（3D）结构，包括带有足细胞的肾小球、肾小管和分支输尿管。为了从PSC再生出功能完善的复杂肾脏，需要广泛研究诱导其余肾祖细胞（即来自PSC的基质祖细胞和重建肾脏的进一步成熟）。除了正确诱导肾祖细胞外，脱细胞和3D生物打印等新的生物工程方法以及其他物种肾脏再生的最新进展，为再生包括人类血管网络和尿液排泄途径在内的复杂肾脏空间排列带来了有希望的线索。
