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中华细胞与干细胞杂志(电子版) ›› 2018, Vol. 08 ›› Issue (01) : 49 -52. doi: 10.3877/cma.j.issn.2095-1221.2018.01.009

所属专题: 文献

综述

多能干细胞诱导分化为肾脏类器官的分子机制及应用前景分析
张登禄1, 杜枭航2, 孔峰2, 赵升田3,()   
  1. 1. 250011 济南,山东中医药大学附属医院实验中心;250033 济南,山东省肾脏再生医学省级重点实验室
    2. 250033 济南,山东省肾脏再生医学省级重点实验室
    3. 250011 济南,山东中医药大学附属医院泌尿外科;250033 济南,山东省肾脏再生医学省级重点实验室
  • 收稿日期:2016-09-30 出版日期:2018-02-01
  • 通信作者: 赵升田

Molecular mechanism and application of kidney organoids from pluripotent cells

Denglu Zhang1, Xiaohang Du2, Feng Kong2, Shengtian Zhao3,()   

  1. 1. Central Laboratory, the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, China; Key Laboratory of Kidney Regeneration of Shandong Province, Jinan 250033, China
    2. Key Laboratory of Kidney Regeneration of Shandong Province, Jinan 250033, China
    3. Department of Urology, the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, China; Key Laboratory of Kidney Regeneration of Shandong Province, Jinan 250033, China
  • Received:2016-09-30 Published:2018-02-01
  • Corresponding author: Shengtian Zhao
  • About author:
    Corresponding author: Zhao Shengtian, Email:
引用本文:

张登禄, 杜枭航, 孔峰, 赵升田. 多能干细胞诱导分化为肾脏类器官的分子机制及应用前景分析[J]. 中华细胞与干细胞杂志(电子版), 2018, 08(01): 49-52.

Denglu Zhang, Xiaohang Du, Feng Kong, Shengtian Zhao. Molecular mechanism and application of kidney organoids from pluripotent cells[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2018, 08(01): 49-52.

干细胞具有自我更新和多向分化潜能,在再生医学领域发挥着越来越大的作用。肾脏类器官是一种由干细胞分化而来具有一定肾脏功能的组织结构,可用于肾脏疾病的细胞修复治疗,也可以模拟肾脏发育和疾病发生及用于筛选改善肾功能的药物。肾脏类器官的体外培育成为了当前研究热点,其体外培育可分为几个阶段:干细胞-原始体节中胚层-中间中胚层-输尿管芽(后肾间质)-集合管(肾单位)。本文重点介绍了目前两种较为成熟的肾脏类器官体外诱导方法,并对肾脏类器官的应用前景进行了综述。

Stem cells with the potential of self-renewal and multilineage differentiation play an increasingly important role in the field of regenerative medicine. Kidney organoids, a kind of tissue structure with certain renal function that derived from stem cells, could be used for cell repair therapy of renal diseases, or for imitating kidney development and disease occurrence so as to screen the drugs which could improve renal function. The culture of kidney organoids in vitro becomes a research hotspot at present. The in vitro culture could be divided into several stages as follows: stem cells-primordial somatic mesoderm-intermediate mesoderm-ureteric bud/metanephric mesenchyme-collecting tube/nephron. Two kinds of more mature in vitro induction methods of kidney organoids at present are focused on and the application prospect of kidney organoids are reviewed.

图1 肾脏类器官诱导过程中主要信号通路
1
Radhakrishnan J, Remuzzi G, Saran R, et al. Taming the chronic kidney disease epidemic: a global view of surveillance efforts[J]. Kidney Int, 2014, 86(2):246-250.
2
Little MH, Mcmahon AP. Mammalian kidney development: principles, progress, and projections[J]. Cold Spring Harb Perspect Biol, 2012, 4(5).
3
Kobayashi A, Valerius MT, Mugford JW, et al. Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development[J]. Cell Stem Cell, 2008, 3(2):169-181.
4
Carroll TJ, Park JS, Hayashi S, et al. Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system[J]. Dev Cell, 2005, 9(2):283-292.
5
Takasato M, Er PX, Chiu HS, et al. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis[J]. Nature, 2015, 526(7574):564-568.
6
Morizane R, Lam AQ, Freedman BS, et al. Nephron organoids derived from human pluripotent stem cells model kidney development and injury[J]. Nat Biotechnol, 2015, 33(11):1193-1200.
7
Taguchi A, Kaku Y, Ohmori T, et al. Redefining the in vivo origin of metanephric nephron progenitors enables Generation of complex kidney structures from pluripotent stem cells[J]. Cell Stem Cell, 2014, 14(1):53-67.
8
Gadue P, Huber TL, Paddison PJ, et al. Wnt and TGF-beta signaling are required for the induction of an in vitro model of primitive streak formation using embryonic stem cells[J]. Proc Natl Acad Sci U S A, 2006, 103(45):16806-16811.
9
Soares ML, Haraguchi S, Torres-Padilla ME, et al. Functional studies of signaling pathways in peri-implantation development of the mouse embryo by RNAi[J]. BMC Dev Biol, 2005, 5:28.
10
Sumi T, Tsuneyoshi N, Nakatsuji N, et al. Defining early lineage specification of human embryonic stem cells by the orchestrated balance of canonical Wnt/beta-catenin, Activin/Nodal and BMP signaling[J]. Development, 2008, 135(17):2969-2979.
11
Mae S, Shono A, Shiota F, et al. Monitoring and robust induction of nephrogenic intermediate mesoderm from human pluripotent stem cells[J]. Nat Commun, 2013, 4:1367.
12
James RG, Kamei CN, Wang Q, et al. Odd-skipped related 1 is required for development of the metanephric kidney and regulates formation and differentiation of kidney precursor cells[J]. Development, 2006, 133(15):2995-3004.
13
Tsang TE, Shawlot W, Kinder SJ, et al. Lim1 activity is required for intermediate mesoderm differentiation in the mouse embryo[J]. Dev Biol, 2000, 223(1):77-90.
14
Crossley PH, Martin GR. The mouse Fgf8 gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo[J]. Development, 1995, 121(2):439-451.
15
Colvin JS, Feldman B, Nadeau JH, et al. Genomic organization and embryonic expression of the mouse fibroblast growth factor 9 gene[J]. Dev Dyn, 1999, 216(1):72-88.
16
Takasato M, Er PX, Becroft M, et al. Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney[J]. Nat Cell Biol, 2014, 16(1):118-126.
17
Rosselot C, Spraggon L, Chia I, et al. Non-cell-autonomous retinoid signaling is crucial for renal development[J]. Development, 2010, 137(2):283-292.
18
Kim D, Dressler GR. Nephrogenic factors promote differentiation of mouse embryonic stem cells into renal epithelia[J]. J Am Soc Nephrol, 2005, 16(12):3527-3534.
19
Barak H, Huh SH, Chen S, et al. FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man[J]. Dev Cell, 2012, 22(6):1191-1207.
20
Tiong HY, Huang P, Xiong S, et al. Drug-induced nephrotoxicity: clinical impact and preclinical in vitro models[J]. Mol Pharm, 2014, 11(7):1933-1948.
21
Li Y, Kandasamy K, Chuah JK, et al. Identification of nephrotoxic compounds with embryonic stem-cell-derived human renal proximal tubular-like cells[J]. Mol Pharm, 2014, 11(7):1982-1990.
22
Bartfeld S, Bayram T, van de Wetering M, et al. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection[J]. Gastroenterology, 2015, 148(1): 126-136.e6.
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