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中华细胞与干细胞杂志(电子版) ›› 2021, Vol. 11 ›› Issue (01) : 57 -62. doi: 10.3877/cma.j.issn.2095-1221.2021.01.009

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综述

多能干细胞诱导分化为肾脏类器官的研究进展与挑战
刘艺霖1, 吴志鹏1, 邱江2,()   
  1. 1. 510080 广州,中山大学附属第一医院器官移植科;510080 广州,华越肾科再生医学科技有限公司
    2. 510080 广州,中山大学附属第一医院器官移植科
  • 收稿日期:2020-08-14 出版日期:2021-02-01
  • 通信作者: 邱江
  • 基金资助:
    广东省自然科学基金(2016A030313190)

Research progress and challenges of differentiation of pluripotent stem cells into kidney organoids

Yilin Liu1, Zhipeng Wu1, Jiang Qiu2,()   

  1. 1. Department of Organ Transplantation, the First Affiliated Hospital of Sun Yat sen University, Guangzhou 510080, China; Asia Kidney Regenerative Medicine Technology Limited, Guangzhou 510080, China
    2. Department of Organ Transplantation, the First Affiliated Hospital of Sun Yat sen University, Guangzhou 510080, China
  • Received:2020-08-14 Published:2021-02-01
  • Corresponding author: Jiang Qiu
引用本文:

刘艺霖, 吴志鹏, 邱江. 多能干细胞诱导分化为肾脏类器官的研究进展与挑战[J/OL]. 中华细胞与干细胞杂志(电子版), 2021, 11(01): 57-62.

Yilin Liu, Zhipeng Wu, Jiang Qiu. Research progress and challenges of differentiation of pluripotent stem cells into kidney organoids[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2021, 11(01): 57-62.

用于分化为多种类型细胞的多能干细胞(PSC)体外培养技术已被广泛应用于生物学领域中。由PSC分化而来的肾脏类器官可基本还原生物体内肾脏的组织结构和部分功能,在肾脏疾病模型研究和药物筛选中有重要作用,继续改善肾脏类器官的结构、功能和成熟度将会对肾脏再生治疗提供极大的帮助。研究肾脏类器官的重点在于体外准确模拟体内肾脏的发育过程。本文着重归纳了近十年来对胚胎肾发育过程研究的重点,对肾脏类器官分化技术的几个关键方案进行总结、分析和比较,并探讨肾脏类器官在分化研究和应用中将面临的挑战。

In biology, in vitro culture of pluripotent stem cells has been widely used to differentiate into various types of cells. Kidney organs derived from pluripotent stem cells can basically restore the tissue structure and partial function of kidney. It plays an important role in the research of kidney disease model and drug screening, and helps to improve the structure, function and maturity of kidney like organs, and is helpful to the treatment of kidney regeneration. Accurate simulation of kidney development in vitro is the focus in kidney organ research. The key point in kidney organoids study is to accurately simulate the development process of kidney in vitro. In this review, we summarize, analyze, and compare key points for kidney organoid differentiation techniques with focus on the process of embryonic kidney development over the past decade, and discuss the challenges for kidney organoids in differentiation research and applications.

1
Clevers H. Modeling development and disease with organoids[J]. Cell, 2016, 165(7):1586-1597.
2
Zhang L, Zhao MH, Zuo L, et al. China Kidney Disease Network (CK-NET) 2015 annual data report[J]. Kidney Int Suppl (2011), 2019, 9(1):e1-e81.
3
Romagnani P. Toward the identification of a "renopoietic system"?[J]. Stem Cells, 2009, 27(9):2247-2253.
4
Park JS, Valerius MT, McMahon AP. Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development[J]. Development, 2007, 134(13):2533-2539.
5
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.
6
Lengerke C, Schmitt S, Bowman TV, et al. BMP and Wnt specify hematopoietic fate by activation of the Cdx-Hox pathway[J]. Cell Stem Cell, 2008, 2(1):72-82.
7
Liu P, Wakamiya M, Shea MJ, et al. Requirement for Wnt3 in vertebrate axis formation[J]. Nat Genet, 1999, 22(4):361-365.
8
Yamaguchi TP, Takada S, Yoshikawa Y, et al. T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification[J]. Genes Dev, 1999, 13(24):3185-3190.
9
Mugford JW, Sipilä P, McMahon JA, et al. Osr1 expression demarcates a multi-potent population of intermediate mesoderm that undergoes progressive restriction to an Osr1-dependent nephron progenitor compartment within the mammalian kidney[J]. Dev Biol, 2008, 324(1):88-98.
10
Saxén L, Sariola H. Early organogenesis of the kidney[J]. Pediatr Nephrol, 1987, 1(3):385-392.
11
Mugford JW, Sipilä P, Kobayashi A, et al. Hoxd11 specifies a program of metanephric kidney development within the intermediate mesoderm of the mouse embryo[J]. Dev Biol, 2008, 319(2):396-405.
12
Boyle S, Misfeldt A, Chandler KJ, et al. Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia[J]. Dev Biol, 2008, 313(1):234-245.
13
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.
14
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.
15
Kispert A, Vainio S, McMahon AP. Wnt-4 is a mesenchymal signal for epithelial transformation of metanephric mesenchyme in the developing kidney[J]. Development, 1998, 125(21):4225-4234.
16
Little MH. Improving our resolution of kidney morphogenesis across time and space[J]. Curr Opin Genet Dev, 2015, 32:135-143.
17
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.
18
Georgas K, Rumballe B, Valerius MT, et al. Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment[J]. Dev Biol, 2009, 332(2):273-286.
19
Kuure S, Popsueva A, Jakobson M, et al. Glycogen synthase kinase-3 inactivation and stabilization of beta-catenin induce nephron differentiation in isolated mouse and rat kidney mesenchymes[J]. J Am Soc Nephrol, 2007, 18(4):1130-1139.
20
Chung E, Deacon P, Marable S, et al. Notch signaling promotes nephrogenesis by downregulating Six2[J]. Development, 2016, 143(21):3907-3913.
21
Deacon P, Concodora CW, Chung E, et al. β-catenin regulates the formation of multiple nephron segments in the mouse kidney[J]. Sci Rep, 2019, 9(1):15915.
22
Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts[J]. Science, 1998, 282(5391):1145-1147.
23
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors[J]. Cell, 2006, 126(4):663-676.
24
Morizane R, Monkawa T, Itoh H. Differentiation of murine embryonic stem and induced pluripotent stem cells to renal lineage in vitro[J]. Biochem Biophys Res Commun, 2009, 390(4):1334-1339.
25
Song B, Smink AM, Jones CV, et al. The directed differentiation of human iPS cells into kidney podocytes[J]. PLoS One, 2012, 7(9):e46453.
26
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.
27
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.
28
肖枫林,李清刚,傅博, 等. 骨髓间充质干细胞构建类肾器官实验[J]. 解放军医学院学报, 2017, 38(10):964-967.
29
肖枫林,王圣元,李明旭. FGF9和CHIR99021诱导胚胎干细胞形成肾脏样结构[J]. 基础医学与临床, 2018, 38(6):759-763.
30
张建烨,管勇,孔峰, 等. 间介中胚层样细胞在肾脏再生中的应用[J]. 中国医学科学院学报, 2019, 41(3):291-299.
31
Freedman BS, Brooks CR, Lam AQ, et al. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids[J]. Nat Commun, 2015, 6:8715.
32
Czerniecki SM, Cruz NM, Harder JL, et al. High-throughput screening enhances kidney organoid differentiation from human pluripotent stem cells and enables automated multidimensional phenotyping[J]. Cell Stem Cell, 2018, 22(6):929-940.e4.
33
Cruz NM, Freedman BS. Differentiation of human kidney organoids from pluripotent stem cells[J]. Methods Cell Biol, 2019, 153:133-150.
34
Morizane R, Bonventre JV. Kidney Organoids: a translational journey[J]. Trends Mol Med. 2017, 23(3):246-263.
35
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.
36
Taguchi A, Nishinakamura R. Higher-order kidney organogenesis from pluripotent stem cells[J]. Cell Stem Cell, 2017, 21(6):730-746.e6.
37
Low JH, Li P, Chew EGY, et al. Generation of human PSC-derived kidney organoids with patterned nephron segments and a De Novo vascular network[J]. Cell Stem Cell, 2019, 25(3):373-387.e9.
38
Dayem AA, Lee SB, Kim K, et al. Recent advances in organoid culture for insulin production and diabetes therapy: methods and challenges[J]. BMB Rep, 2019, 52(5):295-303.
39
Prior N, Inacio P, Huch M. Liver organoids: from basic research to therapeutic applications[J]. Gut, 2019, 68(12):2228-2237.
40
Miyoshi T, Hiratsuka K, Saiz EG, et al. Kidney organoids in translational medicine: disease modeling and regenerative medicine[J]. Dev Dyn, 2020, 249(1):34-45.
41
Freedman BS, Lam AQ, Sundsbak JL, et al. Reduced ciliary polycystin-2 in induced pluripotent stem cells from polycystic kidney disease patients with PKD1 mutations[J]. J Am Soc Nephrol, 2013, 24(10):1571-1586.
42
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.
43
Hale LJ, Howden SE, Phipson B, et al. 3D organoid-derived human glomeruli for personalised podocyte disease modelling and drug screening[J]. Nat Commun, 2018, 9(1):5167.
44
Bantounas I, Ranjzad P, Tengku F, et al. Generation of functioning nephrons by implanting human pluripotent stem cell-derived kidney progenitors[J]. Stem Cell Reports, 2018, 10(3):766-779.
45
Yamanaka S, Tajiri S, Fujimoto T, et al. Generation of interspecies limited chimeric nephrons using a conditional nephron progenitor cell replacement system[J]. Nat Commun, 2017, 8(1):1719.
46
Little MH, Combes AN. Kidney organoids: accurate models or fortunate accidents[J]. Genes Dev, 2019, 33(19-20):1319-1345.
47
Combes AN, Zappia L, Er PX, et al. Single-cell analysis reveals congruence between kidney organoids and human fetal kidney[J]. Genome Med, 2019, 11(1):3.
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