Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, Torino 10126, Italy.
Department of Medical Sciences, University of Torino, Via Nizza 52, Torino 10126, Italy.
Nat Rev Nephrol. 2015 Dec;11(12):695-706. doi: 10.1038/nrneph.2015.126. Epub 2015 Aug 4.
The ability of the human kidney to repair itself is limited. Consequently, repeated injury can trigger a maladaptive response that is characterized by fibrosis and loss of renal function. The transcription patterns that characterize nephrogenesis in fetal renal progenitor cells (RPCs) are only partially activated during renal repair in adults. Nevertheless, evidence suggests that segment-restricted progenitor resident cells support renal healing in adults. In this Review, we discuss the evidence for the existence of functional human RPCs in adults and their role in renal repair, and consider the controversial issue of whether RPCs are a fixed population or arise through phenotypical plasticity of tubular cells that is mediated by the microenvironment. We also discuss the strategies for generating renal progenitor cells from pluripotent stem cells or differentiated cells and their use in therapy. Finally, we examine preclinical data on the therapeutic use of human fetal cells, adult progenitor cells and adult renal cells.
人类肾脏自我修复的能力是有限的。因此,反复的损伤会引发一种适应性不良的反应,其特征是纤维化和肾功能丧失。在胎儿肾祖细胞 (RPC) 中,特征性的肾发生转录模式在成人的肾脏修复过程中仅部分被激活。然而,有证据表明,节段特异性祖细胞驻留细胞支持成人的肾脏愈合。在这篇综述中,我们讨论了在成人中存在功能性人类 RPC 及其在肾脏修复中的作用的证据,并考虑了关于 RPC 是固定群体还是由微环境介导的管状细胞表型可塑性产生的有争议的问题。我们还讨论了从多能干细胞或分化细胞中生成肾祖细胞的策略及其在治疗中的应用。最后,我们研究了关于人类胎儿细胞、成人祖细胞和成人肾细胞治疗用途的临床前数据。