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肾系细胞作为肾脏再生的来源。

Renal lineage cells as a source for renal regeneration.

机构信息

Pediatric Stem Cell Research Institute and Division of Pediatric Nephrology, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

出版信息

Pediatr Res. 2018 Jan;83(1-2):267-274. doi: 10.1038/pr.2017.255. Epub 2017 Nov 15.

Abstract

The mammalian kidney is a highly complex organ, composed of various cell types within a unique structural framework. Nonetheless, in recent years, giant leaps in our understanding of nephrogenesis and the origin of new cells in the adult kidney have resulted in novel routes to regenerate damaged nephrons. While several strategies can be envisioned to achieve this aim, one common theme is the reliance on renal lineage cells, as extrarenal cells, such as bone marrow-derived cells, have been shown to be devoid of renal differentiation capacity. Herein, we will present the main motivation for the pursuit for cell-based therapies, which is the ever growing problem of chronic kidney disease (CKD), and discuss different strategies toward replenishing the damaged renal parenchyma. These include transplantation of fetal kidney grafts or fetal kidney stem cells, directed differentiation of pluripotent stem cells into kidney epithelia, establishment of renal progenitors from the adult kidney, and genetic reprogramming of mature kidney cells into a progenitor state. Taken together with novel techniques recapitulating the three-dimensional developmental environment, these advances are expected to take the field into a new era, bringing us closer than ever to the day when kidney stem cell-based therapy becomes a viable therapeutic option.

摘要

哺乳动物的肾脏是一个高度复杂的器官,由各种细胞类型组成,存在于独特的结构框架内。尽管如此,近年来,我们对肾发生和成年肾脏中新细胞起源的理解取得了巨大的飞跃,从而产生了新的途径来再生受损的肾单位。虽然可以设想几种策略来实现这一目标,但一个共同的主题是依赖于肾谱系细胞,因为已经证明肾外细胞,如骨髓来源的细胞,缺乏肾分化能力。在此,我们将介绍追求基于细胞的治疗的主要动机,即慢性肾脏病 (CKD) 日益严重的问题,并讨论补充受损肾实质的不同策略。这些策略包括移植胎儿肾移植物或胎儿肾干细胞、诱导多能干细胞定向分化为肾上皮细胞、从成人肾脏中建立肾祖细胞,以及将成熟肾脏细胞基因重编程为祖细胞状态。与模拟三维发育环境的新技术相结合,这些进展有望将该领域带入一个新时代,使我们比以往任何时候都更接近基于肾脏干细胞治疗成为可行治疗选择的那一天。

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