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Evolving technology: creating kidney organoids from stem cells

  • Received: 25 May 2016 Accepted: 22 July 2016 Published: 25 July 2016
  • The kidney is a complex organ whose excretory and regulatory functions are vital for maintaining homeostasis. Previous techniques used to study the kidney, including various animal models and 2D cell culture systems to investigate the mechanisms of renal development and regeneration have many benefits but also possess inherent shortcomings. Some of those limitations can be addressed using the emerging technology of 3D organoids. An organoid is a 3D cluster of differentiated cells that are developed ex vivo by addition of various growth factors that result in a miniature organ containing structures present in the tissue of origin. Here, we discuss renal organoids, their development, and how they can be employed to further understand kidney development and disease.

    Citation: Joseph M. Chambers, Robert A. McKee, Bridgette E. Drummond, Rebecca A. Wingert. Evolving technology: creating kidney organoids from stem cells[J]. AIMS Bioengineering, 2016, 3(3): 305-318. doi: 10.3934/bioeng.2016.3.305

    Related Papers:

  • The kidney is a complex organ whose excretory and regulatory functions are vital for maintaining homeostasis. Previous techniques used to study the kidney, including various animal models and 2D cell culture systems to investigate the mechanisms of renal development and regeneration have many benefits but also possess inherent shortcomings. Some of those limitations can be addressed using the emerging technology of 3D organoids. An organoid is a 3D cluster of differentiated cells that are developed ex vivo by addition of various growth factors that result in a miniature organ containing structures present in the tissue of origin. Here, we discuss renal organoids, their development, and how they can be employed to further understand kidney development and disease.


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    [1] McCampbell KK, Wingert RA (2012). Renal stem cells: fact or science fiction? Biochem J 444: 153–168. doi: 10.1042/BJ20120176
    [2] Li Y, Wingert RA (2008) Regenerative medicine for the kidney: stem cell prospects & challenges. Clin Transl Med 2: 11.
    [3] Takasato M, Pei XE, Chiu HS, et al. (2015). Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature 526: 564–568. doi: 10.1038/nature15695
    [4] Dressler GR (2009) Advances in early kidney specification, development and patterning. Development 136: 3863–3874. doi: 10.1242/dev.034876
    [5] Ranghini E, Mora CF, Edgar D et al. (2013) Stem cells derived from neonatal mouse kidney generate functional proximal tubule-like cells and integrate into developing nephrons in vitro. PLoS ONE 8: e62953. doi: 10.1371/journal.pone.0062953
    [6] Georgas K, Rumballe B, Valerius MT, et al. (2009). 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. Dev Biol 332: 273–286. doi: 10.1016/j.ydbio.2009.05.578
    [7] Little MH, McMahon AP (2012) Mammalian kidney development: principles, progress, and projections. Cold Spring Harb Perspect Biol 4: p.a008300.
    [8] Drummond BE, Wingert RA (2016) Insights into kidney stem cell development and regeneration using zebrafish. World J Stem Cells 8: 22–31. doi: 10.4252/wjsc.v8.i2.22
    [9] Takasato M, Little MH (2015) The origin of the mammalian kidney: implications for recreating the kidney in vitro. Development 142: 1937–1947. doi: 10.1242/dev.104802
    [10] DesRochers TM, Suter L, Roth A, et al. (2013) Bioengineered 3D human kidney tissue, a platform for the determination of nephrotoxicity. PLoS ONE 8: e59219. doi: 10.1371/journal.pone.0059219
    [11] DiMasi JA, Hansen RW, Grabowski HG (2003) The price of innovation: new estimates of drug development costs. J Health Econ 22: 151–185.
    [12] DiMasi JA, Grabowski HG, Hansen RW (2016) Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ 47: 20–33. doi: 10.1016/j.jhealeco.2016.01.012
    [13] Fuchs TC, Hewitt P (2011) Biomarkers for drug-induced renal damage and nephrotoxicity—an overview for applied toxicology. AAPS J 13: 615–631.
    [14] Pannu N, Nadim MK (2008) An overview of drug-induced acute kidney injury. Crit Care Med 36: S216–S223. doi: 10.1097/CCM.0b013e318168e375
    [15] Guo Q, Xia B, Moshiach S, et al. (2008) The microenvironmental determinants for kidney epithelial cyst morphogenesis. Eur J Cell Biol 8787: 251–266.
    [16] El Mouedden M, Laurent G, Mingeot-Leclercq MP, et al., (2000) Gentamicin-induced apoptosis in renal cell lines and embryonic rat fibroblasts. Toxicol Sci 56: 229–239. doi: 10.1093/toxsci/56.1.229
    [17] Wu Y, Connors D, Barber L, et al. (2009) Multiplexed assay panel of cytotoxicity in HK-2 cells for detection of renal proximal tubule injury potential of compounds. Toxicol in Vitro 23: 1170–1178. doi: 10.1016/j.tiv.2009.06.003
    [18] Jenkinson SE, Chung GW, van Loon E, et al. (2012). The limitations of renal epithelial cell line HK-2 as a model of drug transporter expression and function in the proximal tubule. Pflügers Arch 464: 601–611.
    [19] Huang JX, Kaeslin G, Ranall MV, et al. (2015) Evaluation of biomarkers for in vitro prediction of drug‐induced nephrotoxicity: comparison of HK‐2, immortalized human proximal tubule epithelial, and primary cultures of human proximal tubular cells. Pharmacol Res Perspect 3: e00148. doi: 10.1002/prp2.148
    [20] Greek R, Menache A (2013) Systematic reviews of animal models: methodology versus epistemology. Int J Med Sci 10: 206–21. doi: 10.7150/ijms.5529
    [21] Grover JW (1961). The enzymatic dissociation and reproducible reaggregation in vitro of 11-day embryonic chick lung. Dev Biol 3: 555–568. doi: 10.1016/0012-1606(61)90032-X
    [22] Fehrenbach ML, Cao G, Williams JT, et al. (2009) Isolation of murine lung endothelial cells. Am J Physiol Lung Cell Mol Physiol 296: L1096–L1103.
    [23] Nag AC, Zak R (1979) Dissociation of adult mammalian heart into single cell suspension: an ultrastructural study. J Anat 129: 541.
    [24] Evans GS, Flint N, Somers AS, et al. (1992) The development of a method for the preparation of rat intestinal epithelial cell primary cultures. J Cell Sci 101: 219–231.
    [25] Fukamachi H (1992) Proliferation and differentiation of fetal rat intestinal epithelial cells in primary serum-free culture. J Cell Sci 103: 511–519.
    [26] Sato T, Vries RG, Snippert HJ, et al. (2009) Single Lgr5 stem cells build crypt villus structures in vitro without a mesenchymal niche. Nature 459: 262–265. doi: 10.1038/nature07935
    [27] Zheng Y, Du X, Wang W, et al. (2005) Organogenesis from dissociated cells: generation of mature cycling hair follicles from skin-derived cells. J Invest Dermatol 124: 867–876. doi: 10.1111/j.0022-202X.2005.23716.x
    [28] Zheng Y, Nace A, Chen W, et al. (2010) Mature hair follicles generated from dissociated cells: a universal mechanism of folliculoneogenesis. Dev Dyn 239: 2619–2626. doi: 10.1002/dvdy.22398
    [29] Unbekandt M, Davies JA (2010) Dissociation of embryonic kidneys followed by reaggregation allows the formation of renal tissues. Kidney Int 77: 407–416. doi: 10.1038/ki.2009.482
    [30] Kreidberg JA, Sariola H, Loring JM, et al. (1993) WT-1 is required for early kidney development. Cell 74: 679–691. doi: 10.1016/0092-8674(93)90515-R
    [31] Davies JA, Ladomery M, Hohenstein P, et al. (2004) Development of an siRNA-based method for repressing specific genes in renal organ culture and its use to show that the Wt1 tumour suppressor is required for nephron differentiation. Human Mol Genet 13: 235–246.
    [32] Xinaris C, Benedetti V, Rizzo P, et al. (2012) In vivo maturation of functional renal organoids formed from embryonic cell suspensions. J Am Soc Nephrol 23: 1857–1868. doi: 10.1681/ASN.2012050505
    [33] Xinaris C, Benedetti V, Novelli R, et al. (2016) Functional human podocytes generated in organoids from amniotic fluid stem cells. J Am Soc Nephrol 27: 1400–1411. doi: 10.1681/ASN.2015030316
    [34] Pavenstädt H, Kriz W, Kretzler M (2003) Cell biology of the glomerular podocyte. Physiol Rev 83: 253–307. doi: 10.1152/physrev.00020.2002
    [35] Xia Y, Nivet E, Sancho-Martinez I, et al. (2013). Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells. Nat Cell Biol 15: 1507–1515. doi: 10.1038/ncb2872
    [36] Lam AQ, Freedman BS, Morizane R, et al. (2013). Rapid and efficient differentiation of human pluripotent stem cells into intermediate mesoderm that forms tubules expressing kidney proximal tubular markers. J Am Soc Nephrol 25: 1211–1225.
    [37] Morizane R, Lam AQ, Freedman BS, et al. (2015) Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nat Biotechnol 33: 1193–1200.
    [38] Takasato M, Er PX, Becroft M, et al. (2014) Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney. Nat Cell Biol 16: 118–126.
    [39] Davies JA (2015) Self-organized kidney rudiments: prospects for better in vitro nephrotoxicity assays. Biomark Insights 10: 117–123.
    [40] Astashkina AI, Mann BK, Prestwich GD, et al. (2012) Comparing predictive drug nephrotoxicity biomarkers in kidney 3-D primary organoid culture and immortalized cell lines. Biomaterials 33: 4712–4721. doi: 10.1016/j.biomaterials.2012.03.001
    [41] Astashkina AI, Jones CF, Thiagarajan G, et al. (2014). Nanoparticle toxicity assessment using an in vitro 3-D kidney organoid culture model. Biomaterials 35: 6323–6331. doi: 10.1016/j.biomaterials.2014.04.060
    [42] Batchelder CA, Martinez ML, Duru N, et al. (2015). Three dimensional culture of human renal cell carcinoma organoids. PLoS ONE 10: e0136758
    [43] Schwank G, Koo BK, Sasselli V, et al. (2013) Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell 13: 653–658. doi: 10.1016/j.stem.2013.11.002
    [44] Freedman BS, Brooks CR, Lam AQ, et al. (2015) Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat Commun 6: 8715. doi: 10.1038/ncomms9715
    [45] Morales EE, Wingert RA (2014) Renal stem cell reprogramming: prospects in regenerative medicine. World J Stem Cells 6: 458–466. doi: 10.4252/wjsc.v6.i4.458
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