Login Register Cart 0
Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Advances and Challenges in Kidney Organoids

Author(s): Vikram Sabapathy*, Gabrielle Costlow, Rajkumar Venkatadri, Murat Dogan, Sanjay Kumar and Rahul Sharma

Volume 17, Issue 3, 2022

Published on: 20 December, 2021

Page: [226 - 236] Pages: 11

DOI: 10.2174/1574888X16666210804113626

Price: $65

Open Access Journals Promotions 2
conference banner
Abstract

The advent of organoids has renewed researchers' interest in in vitro cell culture systems. A wide variety of protocols, primarily utilizing pluripotent stem cells, are under development to improve organoid generation to mimic organ development. The complexity of organoids generated is greatly influenced based on the method used. Understanding the process of kidney organoid formation gives developmental insights into how renal cells form, mature, and interact with the adjacent cells to form specific spatiotemporal structural patterns. This knowledge can bridge the gaps in understanding in vivo renal developmental processes. Evaluating genetic and epigenetic signatures in specialized cell types can help interpret the molecular mechanisms governing cell fate. In addition, development in single-cell RNA sequencing, 3D bioprinting and microfluidic technologies has led to better identification and understanding of a variety of cell types during differentiation and designing of complex structures to mimic the conditions in vivo. While several reviews have highlighted the application of kidney organoids, there is no comprehensive review of various methodologies specifically focusing on kidney organoids. This review summarizes the updated differentiation methodologies, applications, and challenges associated with kidney organoids. Here we have comprehensively collated all the different variables influencing the organoid generation.

Keywords: Organoids, kidney, stem cells, differentiation factors, reprogramming, 3D culture.

« Previous Next »
[1]
Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med 1996; 334(22): 1448-60.
[http://dx.doi.org/10.1056/NEJM199605303342207] [PMID: 8618585]
[2]
Little MH, Combes AN. Kidney organoids: Accurate models or fortunate accidents. Genes Dev 2019; 33: 1319-45.
[3]
Nishinakamura R. Human kidney organoids: Progress and remaining challenges. Nat Rev Nephrol 2019; 15: 613-24.
[4]
Clevers H. COVID-19: Organoids go viral. Nat Rev Mol Cell Biol 2020; 21: 355-6.
[5]
Gupta N, Dilmen E, Morizane R. 3D kidney organoids for bench-to-bedside translation. J Mol Med 2021; 99(4): 477-87.
[6]
Shimizu T, Yamagata K, Osafune K. Kidney organoids: Research in developmental biology and emerging applications. Dev Growth Differ 2021; 63(2): 166-77.
[7]
Romero-Guevara R, Ioannides A, Xinaris C. Kidney organoids as disease models: Strengths, weaknesses and perspectives. Front Physiol 2020; 11: 563981.
[8]
Yousef Yengej FA, Jansen J, Rookmaaker MB, Verhaar MC, Clevers H. Kidney organoids and tubuloids. Cells 2020; 9(6): 1326.
[9]
Kim D, Dressler GR. Nephrogenic factors promote differentiation of mouse embryonic stem cells into renal epithelia. J Am Soc Nephrol 2005; 16(12): 3527-34.
[http://dx.doi.org/10.1681/ASN.2005050544] [PMID: 16267156]
[10]
Bouchard M, Souabni A, Mandler M, Neubüser A, Busslinger M. Nephric lineage specification by Pax2 and Pax8. Genes Dev 2002; 16(22): 2958-70.
[http://dx.doi.org/10.1101/gad.240102] [PMID: 12435636]
[11]
Osafune K, Nishinakamura R, Komazaki S, Asashima M. In vitro induction of the pronephric duct in Xenopus explants. Dev Growth Differ 2002; 44(2): 161-7.
[http://dx.doi.org/10.1046/j.1440-169x.2002.00631.x] [PMID: 11940102]
[12]
Stark K, Vainio S, Vassileva G, McMahon AP. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature 1994; 372(6507): 679-83.
[http://dx.doi.org/10.1038/372679a0] [PMID: 7990960]
[13]
Kobayashi T, Tanaka H, Kuwana H, et al. Wnt4-transformed mouse embryonic stem cells differentiate into renal tubular cells. Biochem Biophys Res Commun 2005; 336(2): 585-95.
[http://dx.doi.org/10.1016/j.bbrc.2005.08.136] [PMID: 16140269]
[14]
Yamamoto M, Cui L, Johkura K, et al. Branching ducts similar to mesonephric ducts or ureteric buds in teratomas originating from mouse embryonic stem cells. Am J Physiol Renal Physiol 2006; 290(1): F52-60.
[15]
McMahon JA, Takada S, Zimmerman LB, Fan CM, Harland RM, McMahon AP. Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev 1998; 12(10): 1438-52.
[http://dx.doi.org/10.1101/gad.12.10.1438] [PMID: 9585504]
[16]
Winnier G, Blessing M, Labosky PA, Hogan BLM. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 1995; 9(17): 2105-16.
[http://dx.doi.org/10.1101/gad.9.17.2105] [PMID: 7657163]
[17]
Johansson BM, Wiles MV. Evidence for involvement of activin A and bone morphogenetic protein 4 in mammalian mesoderm and hematopoietic development. Mol Cell Biol 1995; 15(1): 141-51.
[http://dx.doi.org/10.1128/MCB.15.1.141] [PMID: 7799920]
[18]
Park C, Afrikanova I, Chung YS, et al. A hierarchical order of factors in the generation of FLK1- and SCL-expressing hematopoietic and endothelial progenitors from embryonic stem cells. Development 2004; 131(11): 2749-62.
[http://dx.doi.org/10.1242/dev.01130] [PMID: 15148304]
[19]
Bruce SJ, Rea RW, Steptoe AL, Busslinger M, Bertram JF, Perkins AC. In vitro differentiation of murine embryonic stem cells toward a renal lineage. Differentiation 2007; 75(5): 337-49.
[http://dx.doi.org/10.1111/j.1432-0436.2006.00149.x] [PMID: 17286599]
[20]
Torres M, Gómez-Pardo E, Dressler GR, Gruss P. Pax-2 controls multiple steps of urogenital development. Development 1995; 121(12): 4057-65.
[http://dx.doi.org/10.1242/dev.121.12.4057] [PMID: 8575306]
[21]
Nakane A, Kojima Y, Hayashi Y, Kohri K, Masui S, Nishinakamura R. Pax2 overexpression in embryoid bodies induces upregulation of integrin α8 and aquaporin-1. In Vitro Cell Dev Biol Anim 2009; 45(1–2): 62-8.
[http://dx.doi.org/10.1007/s11626-008-9151-8]
[22]
Morizane R, Monkawa T, Itoh H. Differentiation of murine embryonic stem and induced pluripotent stem cells to renal lineage in vitro. Biochem Biophys Res Commun 2009; 390(4): 1334-9.
[http://dx.doi.org/10.1016/j.bbrc.2009.10.148] [PMID: 19883625]
[23]
Majumdar A, Vainio S, Kispert A, McMahon J, McMahon AP. Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development. Development 2003; 130(14): 3175-85.
[http://dx.doi.org/10.1242/dev.00520] [PMID: 12783789]
[24]
Dudley AT, Godin RE, Robertson EJ. Interaction between FGF and BMP signaling pathways regulates development of metanephric mesenchyme. Genes Dev 1999; 13(12): 1601-13.
[http://dx.doi.org/10.1101/gad.13.12.1601] [PMID: 10385628]
[25]
Ying Q-L, Wray J, Nichols J, et al. The ground state of embryonic stem cell self-renewal. Nature 2008; 453(7194): 519-23.
[http://dx.doi.org/10.1038/nature06968] [PMID: 18497825]
[26]
Mae S, Shirasawa S, Yoshie S, et al. Combination of small molecules enhances differentiation of mouse embryonic stem cells into intermediate mesoderm through BMP7-positive cells. Biochem Biophys Res Commun 2010; 393(4): 877-82.
[http://dx.doi.org/10.1016/j.bbrc.2010.02.111] [PMID: 20171952]
[27]
Nishikawa M, Yanagawa N, Kojima N, et al. Stepwise renal lineage differentiation of mouse embryonic stem cells tracing in vivo development. Biochem Biophys Res Commun 2012; 417(2): 897-902.
[http://dx.doi.org/10.1016/j.bbrc.2011.12.071] [PMID: 22209845]
[28]
Price KL, Kolatsi-Joannou M, Mari C, Long DA, Winyard PJD. Lithium induces mesenchymal-epithelial differentiation during human kidney development by activation of the Wnt signalling system. Cell Death Discov 2018; 4(1): 13.
[http://dx.doi.org/10.1038/s41420-017-0021-6] [PMID: 29531810]
[29]
Woolf AS, Kolatsi-Joannou M, Hardman P, et al. Roles of hepatocyte growth factor/scatter factor and the met receptor in the early development of the metanephros. J Cell Biol 1995; 128(1-2): 171-84.
[http://dx.doi.org/10.1083/jcb.128.1.171] [PMID: 7822413]
[30]
Rogers SA, Ryan G, Hammerman MR. Insulin-like growth factors I and II are produced in the metanephros and are required for growth and development in vitro. J Cell Biol 1991; 113(6): 1447-53.
[http://dx.doi.org/10.1083/jcb.113.6.1447] [PMID: 2045421]
[31]
Morizane R, Monkawa T, Fujii S, et al. Kidney specific protein-positive cells derived from embryonic stem cells reproduce tubular structures in vitro and differentiate into renal tubular cells. PLoS One 2013; 8(6): e64843.
[http://dx.doi.org/10.1371/journal.pone.0064843] [PMID: 23755150]
[32]
Shao X, Johnson JE, Richardson JA, Hiesberger T, Igarashi P. A minimal Ksp-cadherin promoter linked to a green fluorescent protein reporter gene exhibits tissue-specific expression in the developing kidney and genitourinary tract. J Am Soc Nephrol 2002; 13(7): 1824-36.
[http://dx.doi.org/10.1097/01.ASN.0000016443.50138.CD] [PMID: 12089378]
[33]
Barak H, Huh SH, Chen S, et al. FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man. Dev Cell 2012; 22(6): 1191-207.
[http://dx.doi.org/10.1016/j.devcel.2012.04.018] [PMID: 22698282]
[34]
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. Cell Stem Cell 2014; 14(1): 53-67.
[http://dx.doi.org/10.1016/j.stem.2013.11.010] [PMID: 24332837]
[35]
Meng P, Zhu M, Ling X, Zhou L. Wnt signaling in kidney: The initiator or terminator? J Mol Med 2020; 98: 1511-23.
[36]
Watanabe K, Ueno M, Kamiya D, et al. A ROCK inhibitor permits survival of dissociated human embryonic stem cells. Nat Biotechnol 2007; 25(6): 681-6.
[http://dx.doi.org/10.1038/nbt1310] [PMID: 17529971]
[37]
Fetahu IS, Höbaus J, Kállay E. Vitamin D and the epigenome. Front Physiol 2014; 5: 164.
[http://dx.doi.org/10.3389/fphys.2014.00164] [PMID: 24808866]
[38]
Kang M, Han YM. Differentiation of human pluripotent stem cells into nephron progenitor cells in a serum and feeder free system. PLoS One 2014; 9(4): e94888.
[http://dx.doi.org/10.1371/journal.pone.0094888] [PMID: 24728509]
[39]
Morizane R, Lam AQ, Freedman BS, Kishi S, Valerius MT, Bonventre JV. Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nat Biotechnol 2015; 33(11): 1193-200.
[http://dx.doi.org/10.1038/nbt.3392] [PMID: 26458176]
[40]
Takasato M, Er PX, Chiu HS, et al. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature 2015; 526(7574): 564-8.
[http://dx.doi.org/10.1038/nature15695] [PMID: 26444236]
[41]
Freedman BS, Brooks CR, Lam AQ, et al. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat Commun 2015; 6(1): 8715.
[http://dx.doi.org/10.1038/ncomms9715] [PMID: 26493500]
[42]
Toyohara T, Mae S, Sueta S, et al. Cell therapy using human induced pluripotent stem cell-derived renal progenitors ameliorates acute kidney injury in mice. Stem Cells Transl Med 2015; 4(9): 980-92.
[http://dx.doi.org/10.5966/sctm.2014-0219] [PMID: 26198166]
[43]
Shankar AS, Du Z, Mora HT, et al. Human kidney organoids produce functional renin. Kidney Int 2021; 99(1): 134-47.
[http://dx.doi.org/10.1016/j.kint.2020.08.008] [PMID: 32918942]
[44]
Uchimura K, Wu H, Yoshimura Y, Humphreys BD. Human pluripotent stem cell-derived kidney organoids with improved collecting duct maturation and injury modeling. Cell Rep 2020; 33(11): 108514.
[http://dx.doi.org/10.1016/j.celrep.2020.108514] [PMID: 33326782]
[45]
Garreta E, Prado P, Tarantino C, et al. Fine tuning the extracellular environment accelerates the derivation of kidney organoids from human pluripotent stem cells. Nat Mater 2019; 18(4): 397-405.
[http://dx.doi.org/10.1038/s41563-019-0287-6] [PMID: 30778227]
[46]
Gupta AK, Coburn JM, Davis-Knowlton J, Kimmerling E, Kaplan DL, Oxburgh L. Scaffolding kidney organoids on silk. J Tissue Eng Regen Med 2019; 13(5): 812-22.
[http://dx.doi.org/10.1002/term.2830] [PMID: 30793851]
[47]
Higgins JW, Chambon A, Bishard K, et al. Bioprinted pluripotent stem cell-derived kidney organoids provide opportunities for high content screening. bioRxiv 2018; 505396.
[48]
Lawlor KT, Vanslambrouck JM, Higgins JW, et al. Cellular extrusion bioprinting improves kidney organoid reproducibility and conformation. Nat Mater 2020; 20(2): 260-71.
[PMID: 33230326]
[49]
Trapnell C, Cacchiarelli D, Grimsby J, et al. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat Biotechnol 2014; 32(4): 381-6.
[http://dx.doi.org/10.1038/nbt.2859] [PMID: 24658644]
[50]
Kumar S V, Er PX, Lawlor KT, et al. Kidney micro-organoids in suspension culture as a scalable source of human pluripotent stem cell-derived kidney cells. Development 2019; 146(5): dev172361.
[http://dx.doi.org/10.1242/dev.172361]
[51]
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. Cell Stem Cell 2018; 22(6): 929-40.e4.
[http://dx.doi.org/10.1016/j.stem.2018.04.022] [PMID: 29779890]
[52]
Nakayama M, Nozu K, Goto Y, et al. HNF1B alterations associated with congenital anomalies of the kidney and urinary tract. Pediatr Nephrol 2010; 25(6): 1073-9.
[http://dx.doi.org/10.1007/s00467-010-1454-9] [PMID: 20155289]
[53]
Przepiorski A, Sander V, Tran T, et al. A simple bioreactor-based method to generate kidney organoids from pluripotent stem cells. Stem Cell Reports 2018; 11(2): 470-84.
[http://dx.doi.org/10.1016/j.stemcr.2018.06.018] [PMID: 30033089]
[54]
Liu E, Radmanesh B, Chung BH, et al. Profiling APOL1 nephropathy risk variants in genome-edited kidney organoids with single-cell transcriptomics. Kidney360 2020; 1(3): 203-15.
[55]
Ajaimy M, Melamed ML. Covid-19 in patients with kidney disease. In: Clin J American Soc Nephrol. 2020; 15: pp. (8)1087-9.
[56]
Mahalingam R, Dharmalingam P, Santhanam A, et al. Single-cell RNA sequencing analysis of SARS-CoV-2 entry receptors in human organoids. J Cell Physiol 2021; 236(4): 2950-8.
[http://dx.doi.org/10.1002/jcp.30054] [PMID: 32944935]
[57]
Monteil V, Kwon H, Prado P, et al. Inhibition of sars-cov-2 infections in engineered human tissues using clinical-grade soluble human ace2. Cell 2020; 181(4): 905-913.e7.
[http://dx.doi.org/10.1016/j.cell.2020.04.004] [PMID: 32333836]
[58]
Calandrini C, Schutgens F, Oka R, et al. An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity. Nat Commun 2020; 11(1): 1310.
[http://dx.doi.org/10.1038/s41467-020-15155-6] [PMID: 32161258]
[59]
Schlieve CR, Fowler KL, Thornton M, et al. Neural crest cell implantation restores enteric nervous system function and alters the gastrointestinal transcriptome in human tissue-engineered small intestine. Stem Cell Reports 2017; 9(3): 883-96.
[http://dx.doi.org/10.1016/j.stemcr.2017.07.017] [PMID: 28803915]
[60]
Homan KA, Gupta N, Kroll KT, et al. Flow-enhanced vascularization and maturation of kidney organoids in vitro. Nat Methods 2019; 16(3): 255-62.
[http://dx.doi.org/10.1038/s41592-019-0325-y] [PMID: 30742039]

Rights & Permissions Print Cite
Article Metrics
68
1
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy