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Stem Cells and Kidney Regeneration

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Pediatric Nephrology

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Abstracts

Because of the few effective treatments for many chronic kidney diseases, increasing consideration has been given to new regenerative therapies using stem cells. Recent advances in developmental biology and stem cell biology have led to the increased availability of renal stem/progenitor cells from multiple sources, including their isolation from embryonic and adult kidneys, and to the generation of kidney lineage cells by the directed differentiation of pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), or by the cellular reprogramming of fully differentiated adult renal cells or across mature lineages. Cell therapies using renal stem/progenitor cells derived from adult and embryonic kidneys or differentiated from ESCs/iPSCs have been investigated in kidney disease models. The reconstruction of transplantable kidney organs is also being attempted using ESC/iPSC-derived kidney lineage cells. Cancer stem cells, which are thought to initiate and maintain malignant tumors, have been identified in renal cell carcinomas (RCC) and in Wilms’ tumor (WT), the most common pediatric renal malignancy. The development of regenerative treatment using stem cells and their bioproducts and targeted therapies against renal cancer stem cells may open new avenues in renal medicine.

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References

  1. GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395(10225):709–33.

    Article  Google Scholar 

  2. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:1145–7.

    Article  CAS  PubMed  Google Scholar 

  3. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72.

    Article  CAS  PubMed  Google Scholar 

  4. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–20.

    Article  CAS  PubMed  Google Scholar 

  5. Little MH, Kumar SV, Forbes T. Recapitulating kidney development: progress and challenges. Semin Cell Dev Biol. 2019;91:153–68.

    Article  CAS  PubMed  Google Scholar 

  6. Little MH. Returning to kidney development to deliver synthetic kidneys. Dev Biol. 2020; S0012-1606(20)30318-3

    Google Scholar 

  7. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367(6464):645–8.

    Article  CAS  PubMed  Google Scholar 

  8. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11.

    Article  CAS  PubMed  Google Scholar 

  9. Ailles LE, Weissman IL. Cancer stem cells in solid tumors. Curr Opin Biotechnol. 2007;18(5):460–6.

    Article  CAS  PubMed  Google Scholar 

  10. Saxen L. Organogenesis of the kidney. Cambridge: Cambridge University Press; 1987.

    Book  Google Scholar 

  11. McMahon AP. Development of the mammalian kidney. Curr Top Dev Biol. 2016;117:31–64.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Mugford JW, Sipilä P, McMahon JA, McMahon AP. 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. Dev Biol. 2008;324:88–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tsujimoto H, Kasahara T, Sueta S, Araoka T, Sakamoto S, Okada C, et al. A modular differentiation system maps multiple human kidney lineage from pluripotent stem cells. Cell Rep. 2020;31(1):107476.

    Article  CAS  PubMed  Google Scholar 

  14. Costantini F, Kopan R. Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development. Dev Cell. 2010;18:698–712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Taguchi A, Kaku Y, Ohmori T, Sharmin S, Ogawa M, Sasaki H, 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;14:53–67.

    Article  CAS  PubMed  Google Scholar 

  16. Kobayashi A, Valerius MT, Mugford JW, Carroll TJ, Self M, Oliver G, et al. Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell. 2008;8:169–81.

    Article  CAS  Google Scholar 

  17. Shakya R, Watanabe T, Costantini F. The role of GDNF/Ret signaling in ureteric bud cell fate and branching morphogenesis. Dev Cell. 2005;8:65–74.

    Article  CAS  PubMed  Google Scholar 

  18. Carroll TJ, Park JS, Hayashi S, Majumdar A, McMahon AP. Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system. Dev Cell. 2005;9:283–92.

    Article  CAS  PubMed  Google Scholar 

  19. Stark K, Vainio S, Vassileva G, McMahon AP. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature. 1994;372:679–83.

    Article  CAS  PubMed  Google Scholar 

  20. Barak H, Huh SH, Chen S, Jeanpierre C, Martinovic J, Parisot M, et al. FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man. Dev Cell. 2012;22:1191–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Poladia DP, Kish K, Kutay B, Hains D, Kegg H, Zhao H, et al. Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme. Dev Biol. 2006;291:325–39.

    Article  CAS  PubMed  Google Scholar 

  22. Humphreys BD, Valerius MT, Kobayashi A, Mugford JW, Soeung S, Duffield JS, et al. Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell. 2008;2:284–91.

    Article  CAS  PubMed  Google Scholar 

  23. Diep CQ, Ma D, Deo RC, Holm TM, Naylor RW, Arora N, et al. Identification of adult nephron progenitors capable of kidney regeneration in zebrafish. Nature. 2011;470:95–100.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Singh SR, Liu W, Hou SX. The adult Drosophila malpighian tubules are main-tained by multipotent stem cells. Cell Stem Cell. 2007;1:191–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hatini V, Huh SO, Herzlinger D, Soares VC, Lai E. Essential role of stromal mesenchyme in kidney morphogenesis revealed by targeted disruption of Winged Helix transcription factor BF-2. Genes Dev. 1996;10:1467–78.

    Article  CAS  PubMed  Google Scholar 

  26. Mendelsohn C, Batourina E, Fung S, Gilbert T, Dodd J. Stromal cells mediate retinoid-dependent functions essential for renal development. Development. 1999;126:1139–48.

    Article  CAS  PubMed  Google Scholar 

  27. Dudley AT, Godin RE, Robertson EJ. Interaction between FGF and BMP signaling pathways regulates development of metanephric mesenchyme. Genes Dev. 1999;13:1601–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kobayashi A, Mugford JW, Krautzberger AM, Naiman N, Liao J, McMahon AP. Identification of a multipotent self-renewing stromal progenitor population during mammalian kidney organogenesis. Stem Cell Rep. 2014;3(4):650–62.

    Article  CAS  Google Scholar 

  29. Hammerman MR. Transplantation of renal precursor cells: a new therapeutic approach. Pediatr Nephrol. 2000;14:513–7.

    Article  CAS  PubMed  Google Scholar 

  30. Dekel B, Amariglio N, Kaminski N, Schwartz A, Goshen E, Arditti FD, et al. Engraftment and differentiation of human metanephroi into functional mature nephrons after transplantation into mice is accompanied by a profile of gene expression similar to normal human kidney development. J Am Soc Nephrol. 2002;13:977–90.

    Article  CAS  PubMed  Google Scholar 

  31. Dekel B, Burakova T, Arditti FD, Reich-Zeliger S, Milstein O, Aviel-Ronen S, et al. Human and porcine early kidney precursors as a new source for transplantation. Nat Med. 2003;9:53–60.

    Article  CAS  PubMed  Google Scholar 

  32. van den Berg CW, Ritsma L, Avramut MC, Wiersma LE, van den Berg BM, Leuning DG, et al. Renal subcapsular transplantation of PSC-derived kidney organoids induces neo-vasculogenesis and significant glomerular and tubular maturation in vivo. Stem Cell Reports. 2018;10(3):751–65.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Kim SS, Park HJ, Han J, Gwak SJ, Park MH, Song KW, et al. Improvement of kidney failure with fetal kidney precursor cell transplantation. Transplantation. 2007;83(9):1249–58.

    Article  PubMed  Google Scholar 

  34. Osafune K, Takasato M, Kispert A, Asashima M, Nishinakamura R. Identification of multipotent progenitors in the embryonic mouse kidney by a novel colony-forming assay. Development. 2006;133:151–61.

    Article  CAS  PubMed  Google Scholar 

  35. Lusis M, Li J, Ineson J, Christensen ME, Rice A, Little MH. Isolation of clono-genic, long-term self renewing embryonic renal stem cells. Stem Cell Res. 2010;5:23–39.

    Article  CAS  PubMed  Google Scholar 

  36. Brown AC, Muthukrishnan SD, Oxburgh L. A synthetic niche for nephron progenitor cells. Dev Cell. 2015;34(2):229–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Tanigawa S, Taguchi A, Sharma N, Perantoni AO, Nishinakamura R. Selective in vitro propagation of nephron progenitors derived from embryos and pluripotent stem cells. Cell Rep. 2016;15(4):801–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Li Z, Araoka T, Wu J, Liao H, Li M, Lazo M, et al. 3D culture supports long-term expansion of mouse and human nephrogenic progenitors. Cell Stem Cell. 2016;19(4):516–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lazzeri E, Crescioli C, Ronconi E, Mazzinghi B, Sagrinati C, Netti GS, et al. Regenerative potential of embryonic renal multipotent progenitors in acute renal failure. J Am Soc Nephrol. 2007;18(12):3128–38.

    Article  CAS  PubMed  Google Scholar 

  40. Dekel B, Metsuyanim S, Schmidt-Ott KM, Fridman E, Jacob-Hirsch J, SimonA, et al. Multiple imprinted and stemness genes provide a link between normal and tumor progenitor cells of the developing human kidney. Cancer Res. 2006;66:6040–9.

    Article  CAS  PubMed  Google Scholar 

  41. Pode-Shakked N, Metsuyanim S, Rom-Gross E, Mor Y, Fridman E, Goldstein I, et al. Developmental tumourigenesis: NCAM as a putative marker for the malignant renal stem/progenitor cell population. J Cell Mol Med. 2009;13(8B):1792–808.

    Article  PubMed  Google Scholar 

  42. Pleniceanu O, Harari-Steinberg O, Dekel B. Concise review: kidney stem/progenitor cells: differentiate, sort out, or reprogram? Stem Cells. 2010;28:1649–60.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Harari-Steinberg O, Metsuyanim S, Omer D, Gnatek Y, Gershon R, Pri-Chen S, et al. Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease. EMBO Mol Med. 2013;5:1556–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Noiman T, Buzhor E, Metsuyanim S, Harari-Steinberg O, Morgenshtern C, Dekel B, et al. A rapid in vivo assay system for analyzing the organogenetic capacity of human kidney cells. Organogenesis. 2011;7(2):140–4.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Pode-Shakked N, Gershon R, Tam G, Omer D, Gnatek Y, Kanter I, et al. Evidence of in vitro preservation of human nephrogenesis at the single-cell level. Stem Cell Rep. 2017;9(1):279–91.

    Article  CAS  Google Scholar 

  46. Pode-Shakked N, Pleniceanu O, Gershon R, Shukrun R, Kanter I, Bucris E, et al. Dissecting stages of human kidney development and tumorigenesis with surface markers affords simple prospective purification of nephron stem cells. Sci Rep. 2016;6:23562.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Karagiannis P, Takahashi K, Saito M, Yoshida Y, Okita K, Watanabe A, et al. Physiol Rev. 2019;99(1):79–114.

    Article  CAS  PubMed  Google Scholar 

  48. Ilic D, Devito L, Miere C, Codognotto S. Human embryonic and induced pluripotent stem cells in clinical trials. Br Med Bull. 2015;116:19–27.

    PubMed  Google Scholar 

  49. Kim D, Dressler GR. Nephrogenic factors promote differentiation of mouse embryonic stem cells into renal epithelia. J Am Soc Nephrol. 2005;16:3527–34.

    Article  CAS  PubMed  Google Scholar 

  50. Mae S, Shono A, Shiota F, Yasuno T, Kajiwara M, Gotoda-Nishimura N, et al. Monitoring and robust induction of nephrogenic intermediate mesoderm from human pluripotent stem cells. Nat Commun. 2013;4:1367.

    Article  PubMed  CAS  Google Scholar 

  51. Lam AQ, Freedman BS, Morizane R, Lerou PH, Valerius MT, Bonventre JV. Rapid and efficient differentiation of human pluripotent stem cells into intermediate mesoderm that forms tubules expressing kidney proximal tubular markers. J Am Soc Nephrol. 2014;25:1211–25.

    Article  CAS  PubMed  Google Scholar 

  52. Takasato M, Er PX, Chiu HS, Maier B, Baillie GJ, Ferguson C, et al. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature. 2015;526(7574):564–8.

    Article  CAS  PubMed  Google Scholar 

  53. Morizane R, Lam AQ, Freedman BS, Kishi S, Valeius MT, Bonventre JV. Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nat Biotechnol. 2015;33(11):1193–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yoshimura Y, Taguchi A, Tanigawa S, Yatsuda J, Kamba T, Takahashi S, et al. Manipulation of nephron-patterning signals enables selective induction of podocytes from human pluripotent stem cells. J Am Soc Nephrol. 2019;30(2):304–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Xia Y, Nivet E, Sancho-Martinez I, Gallegos T, Suzuki K, Okamura D, et al. Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells. Nat Cell Biol. 2013;15:1507–15.

    Article  CAS  PubMed  Google Scholar 

  56. Taguchi A, Nishinakamura R. Higher-order kidney organogenesis from pluripotent stem cells. Cell Stem Cell. 2017;21(6):730–46.

    Article  CAS  PubMed  Google Scholar 

  57. Mae SI, Ryosaka M, Toyoda T, Matsuse K, Oshima Y, Tsujimoto H, et al. Generation of branching ureteric bud tissues from human pluripotent stem cells. Biochem Biophys Res Commun. 2018;495(1):954–61.

    Article  CAS  PubMed  Google Scholar 

  58. Mae SI, Ryosaka M, Sakamoto S, Matsuse K, Nozaki A, Igami M, et al. Expansion of human iPSC-derived ureteric bud organoids with repeated branching potential. Cell Rep. 2020;32(4):107963.

    Article  CAS  PubMed  Google Scholar 

  59. Sharmin S, Taguchi A, Kaku Y, Yoshimura Y, Ohmori T, Sakuma T, et al. Human induced pluripotent stem cell-derived podocytes mature into vascularized glomeruli upon experimental transplantation. J Am Soc Nephrol. 2016;27:1778–91.

    Article  CAS  PubMed  Google Scholar 

  60. van den Berg BM, Wang G, Boels MGS, Avramut MC, Jansen E, Sol WMPJ, et al. Glomerular function and structural integrity depend on hyaluronan synthesis by glomerular endothelium. J Am Soc Nephrol. 2019;30(10):1886–97.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Bantounas I, Ranjzad P, Tengku F, Silajdžić E, Foster D, Asselin MC, et al. Generation of functioning nephrons by implanting human pluripotent stem cell-derived kidney progenitors. Stem Cell Reports. 2018;10(3):766–79.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Suchy F, Yamaguchi T, Nakauchi H. iPSC-derived organs in vivo: challenges and promise. Cell Stem Cell. 2018;22(1):21–4.

    Article  CAS  PubMed  Google Scholar 

  63. Usui J, Kobayashi T, Yamaguchi T, Knisely AS, Nishinakamura R, Nakauchi H. Generation of kidney from pluripotent stem cells via blastocyst complementation. Am J Pathol. 2012;180:2417–26.

    Article  CAS  PubMed  Google Scholar 

  64. Goto T, Hara H, Sanbo M, Masaki H, Sato H, Yamaguchi T, et al. Generation of pluripotent stem cell-derived mouse kidney in sall1-targeted anephric rats. Nat Commun. 2019;10(1):451.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Yamanaka S, Tajiri S, Fujimoto T, Matsumoto K, Fukunaga S, Kim BS, et al. Generation of interspecies limited chimeric nephrons using a conditional nephron progenitor cell replacement system. Nat Commun. 2017;8(1):1719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Fujimoto T, Yamanaka S, Tajiri S, Takamura T, Saito Y, Matsumoto N, et al. Generation of human renal vesicles in mouse organ niche using nephron progenitor cell replacement system. Cell Rep. 2020;32(11):108130.

    Article  CAS  PubMed  Google Scholar 

  67. Imberti B, Tomasoni S, Ciampi O, Pezzotta A, Derosas M, Xinaris C, et al. Renal progenitors derived from human iPSCs engraft and restore function in a mouse model of acute kidney injury. Sci Rep. 2015;5:8826.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Toyohara T, Mae SI, Sueta SI, Inoue T, Yamagishi Y, Kawamoto T, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kaminski MM, Tosic J, Kresbach C, Engel H, Klockenbusch J, Muller AL, et al. Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors. Nat Cell Biol. 2016;18(12):1269–80.

    Article  CAS  PubMed  Google Scholar 

  70. Hendry CE, Vanslambrouck JM, Ineson J, Suhaimi N, Takasato M, Rae F, et al. Direct transcriptional reprogramming of adult cells to embryonic nephron progenitors. J Am Soc Nephrol. 2013;24:1424–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Vanslambrouck JM, Woodard LE, Suhaimi N, Williams FM, Howden SE, Wilson SB, et al. Direct reprogramming to human nephron progenitor-like cells using inducible piggyBac transposon expression of SNAL2-EYA1-SIX1. Kidney Int. 2019;95(5):1153–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Hiratsuka K, Monkawa T, Akiyama T, Nakatake Y, Oda M, Goparaju SK, et al. Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factor. Sci Rep. 2019;9(1):913.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Omer D, Harari-Steinberg O, Buzhor E, Metsuyanim S, Pleniceanu O, Zundelevich A, et al. Chromatin-modifying agents reactivate embryonic renal stem/progenitor genes in human adult kidney epithelial cells but abrogate dedifferentiation and stemness. Cell Reprogram. 2013;15(4):281–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Till JE, McCulloch EA, Siminovitch L. A stochastic model of stem cell proliferation, based on the growth of spleen colony-forming cells. Proc Natl Acad Sci USA. 1964;51:29–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol. 1966;16(3):381–90.

    CAS  PubMed  Google Scholar 

  76. Pittenger MF, Discher DE, Peault BM, Phinney DG, Hare JM, Caplan A. Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen Med. 2019;4:22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell. 2001;105(3):369–77.

    Article  CAS  PubMed  Google Scholar 

  78. Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature. 2002;416(6880):542–5.

    Article  CAS  PubMed  Google Scholar 

  79. Togel F, Westenfelder C. Mesenchymal stem cells: a new therapeutic tool for AKI. Nat Rev Nephrol. 2010;6(3):179–83.

    Article  PubMed  Google Scholar 

  80. Pleniceanu O, Harari-Steinberg O, Omer D, Gnatek Y, Lachmi BE, Cohen-Zontag O, et al. Successful introduction of human renovascular units into the mammalian kidney. J Am Soc Nephrol. 2020;31(12):2757–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kusaba T, Lalli M, Kramann R, Kobayashi A, Humphreys BD. Differentiated kidney epithelial cells repair injured proximal tubule. Proc Natl Acad Sci USA. 2014;111:1527–32.

    Article  CAS  PubMed  Google Scholar 

  82. Vogetseder A, Picard N, Gaspert A, Walch M, Kaissling B, Le Hir M. Proliferation capacity of the renal proximal tubule involves the bulk of differentiated epithelial cells. Am J Physiol Cell Physiol. 2008;294(1):C22–8.

    Article  CAS  PubMed  Google Scholar 

  83. Vogetseder A, Palan T, Bacic D, Kaissling B, Le Hir M. Proximal tubular epithelial cells are generated by division of differentiated cells in the healthy kidney. Am J Physiol Cell Physiol. 2007;292(2):C807–13.

    Article  CAS  PubMed  Google Scholar 

  84. Berger K, Bangen JM, Hammerich L, Liedtke C, Floege J, Smeets B, et al. Origin of regenerating tubular cells after acute kidney injury. Proc Natl Acad Sci USA. 2014;111(4):1533–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Rinkevich Y, Montoro DT, Contreras-Trujillo H, Harari-Steinberg O, Newman AM, Tsai JM, et al. In vivo clonal analysis reveals lineage-restricted progenitor characteristics in mammalian kidney development, maintenance, and regeneration. Cell Rep. 2014;7(4):1270–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Cohen-Zontag O, Gershon R, Harari-Steinberg O, Kanter I, Omer D, Pleniceanu O, et al. Human kidney clonal proliferation disclose lineage-restricted precursor characteristics. Sci Rep. 2020;10(1):22097.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  87. Anglani F, Mezzabotta F, Ceol M, Cristofaro R, Del Prete D, D’Angelo A. The regenerative potential of the kidney: what can we learn from developmental biology? Stem Cell Rev. 2010;6:650–7.

    Article  Google Scholar 

  88. Maeshima A, Yamashita S, Nojima Y. Identification of renal progenitor-like tubular cells that participate in the regeneration processes of the kidney. J Am Soc Nephrol. 2003;14:3138–46.

    Article  PubMed  Google Scholar 

  89. Oliver JA, Maarouf O, Cheema FH, Martens TP, Al-Awqati Q. The renal papilla is a niche for adult kidney stem cells. J Clin Invest. 2004;114:795–804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Kitamura S, Yamasaki Y, Kinomura M, Sugaya T, Sugiyama H, Maeshima Y, et al. Establishment and characterization of renal progenitor like cells from S3 segment of nephron in rat adult kidney. FASEB J. 2005;19(13):1789–97.

    Article  CAS  PubMed  Google Scholar 

  91. Buzhor E, Harari-Steinberg O, Omer D, Metsuyanim S, Jacob-Hirsch J, Noiman T, et al. Kidney spheroids recapitulate tubular organoids leading to enhanced tubulogenic potency of human kidney-derived cells. Tissue Eng A. 2011;17:2305–19.

    Article  CAS  Google Scholar 

  92. Harari-Steinberg O, Omer D, Gnatek Y, Pleniceanu O, Goldberg S, Cohen-Zontag O, et al. Ex vivo expanded 3D human kidney spheres engraft long term and repair chronic renal injury in mice. Cell Rep. 2020;30(3):852–69.e4.

    Article  CAS  PubMed  Google Scholar 

  93. Bombelli S, Zipeto MA, Torsello B, Bovo G, Di Stefano V, Bugarin C, et al. PKH (high) cells within clonal human nephrospheres provide a purified adult renal stem cell population. Stem Cell Res. 2013;11(3):1163–77.

    Article  CAS  PubMed  Google Scholar 

  94. Bussolati B, Bruno S, Grange C, Buttiglieri S, Deregibus MC, Cantino D, et al. Isolation of renal progenitor cells from adult human kidney. Am J Pathol. 2005;166(2):545–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Dekel B, Zangi L, Shezen E, Reich-Zeliger S, Eventov-Friedman S, Katchman H, et al. Isolation and characterization of nontubular sca-1+lin- multipotent stem/progenitor cells from adult mouse kidney. J Am Soc Nephrol. 2006;17(12):3300–14.

    Article  PubMed  Google Scholar 

  96. Sagrinati C, Netti GS, Mazzinghi B, Lazzeri E, Liotta F, Frosali F, et al. Isolation and characterization of multipotent progenitor cells from the Bowman’s capsule of adult human kidneys. J Am Soc Nephrol. 2006;17(9):2443–56.

    Article  CAS  PubMed  Google Scholar 

  97. Bruno S, Bussolati B, Grange C, Collino F, di Cantogno LV, Herrera MB, et al. Isolation and characterization of resident mesenchymal stem cells in human glomeruli. Stem Cells Dev. 2009;18(6):867–80.

    Article  CAS  PubMed  Google Scholar 

  98. Buzhor E, Omer D, Harari-Steinberg O, Dotan Z, Vax E, Pri-Chen S, et al. Reactivation of NCAM1 defines a subpopulation of human adult kidney epithelial cells with clonogenic and stem/progenitor properties. Am J Pathol. 2013;183(5):1621–33.

    Article  CAS  PubMed  Google Scholar 

  99. Gupta S, Verfaillie C, Chmielewski D, Kren S, Eidman K, Connaire J, et al. Isolation and characterization of kidney-derived stem cells. J Am Soc Nephrol. 2006;17(11):3028–40.

    Article  CAS  PubMed  Google Scholar 

  100. Pippin JW, Sparks MA, Glenn ST, Buitrago S, Coffman TM, Duffield JS, et al. Cells of renin lineage are progenitors of podocytes and parietal epithelial cells in experimental glomerular disease. Am J Pathol. 2013;183(2):542–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Challen GA, Bertoncello I, Deane JA, Ricardo SD, Little MH. Kidney side population reveals multilineage potential and renal functional capacity but also cellular heterogeneity. J Am Soc Nephrol. 2006;17(7):1896–912.

    Article  CAS  PubMed  Google Scholar 

  102. Lee PT, Lin HH, Jiang ST, Lu PJ, Chou KJ, Fang HC, et al. Mouse kidney progenitor cells accelerate renal regeneration and prolong survival after ischemic injury. Stem Cells. 2010;28(3):573–84.

    CAS  PubMed  Google Scholar 

  103. Li J, Ariunbold U, Suhaimi N, Sunn N, Guo J, McMahon JA, et al. Collecting duct-derived cells display mesenchymal stem cell properties and retain selective in vitro and in vivo epithelial capacity. J Am Soc Nephrol. 2014:pii.

    Google Scholar 

  104. Schutgens F, Rookmaaker MB, Margaritis T, Rios A, Ammerlaan C, Jansen J, et al. Tubuloids derived from human adult kidney and urine for personalized disease modeling. Nat Biotechnol. 2019;37(3):303–13.

    Article  CAS  PubMed  Google Scholar 

  105. Scadden DT. The stem-cell niche as an entity of action. Nature. 2006;441(7097):1075–9.

    Article  CAS  PubMed  Google Scholar 

  106. Peired AJ, Sisti A, Romagnani P. Renal cancer stem cells: characterization and targeted therapies. Stem Cells Int. 2016;2016:8342625.

    PubMed  PubMed Central  Google Scholar 

  107. Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L, Schmidinger M, et al. Renal cell carcinoma. Nat Rev Dis Primers. 2017;3:17009.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Bussolati B, Bruno S, Grange C, Ferrando U, Camussi G. Identification of a tumor-initiating stem cell population in human renal carcinomas. FASEB J. 2008;22:3696–705.

    Article  CAS  PubMed  Google Scholar 

  109. Zhong Y, Guan K, Guo S, Zhou C, Wang D, Ma W, et al. Spheres derived from the human SK-RC-42 renal cell carcinoma cell line are enriched in cancer stem cells. Cancer Lett. 2010;299(2):150–60.

    Article  CAS  PubMed  Google Scholar 

  110. Addla SK, Brown MD, Hart CA, Ramani VA, Clarke NW. Characterization of the Hoechst 33342 side population from normal and malignant human renal epithelial cells. Am J Physiol Renal Physiol. 2008;295(3):F680–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Dénes FT, Duarte RJ, Cristófani LM, Lopes RI. Pediatric genitourinary oncology. Front Pediatr. 2013;1:48.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Shukrun R, Pode-Shakked N, Dekel B. Targeted therapy aimed at cancer stem cells: Wilms’ tumor as an example. Pediatr Nephrol. 2014;29(5):815–23.

    Article  PubMed  Google Scholar 

  113. Metsuyanim S, Pode-Shakked N, Schmidt-Ott KM, Keshet G, Rechavi G, Blumental D, et al. Accumulation of malignant renal stem cells is associated with epigenetic changes in normal renal progenitor genes. Stem Cells. 2008;26(7):1808–17.

    Article  CAS  PubMed  Google Scholar 

  114. Aiden AP, Rivera MN, Rheinbay E, Ku M, Coffman EJ, Truong TT, et al. Wilms tumor chromatin profiles highlight stem cell properties and a renal developmental network. Cell Stem Cell. 2010;6(6):591–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Pode-Shakked N, Shukrun R, Mark-Danieli M, Tsvetkov P, Bahar S, Pri-Chen S, et al. The isolation and characterization of renal cancer initiating cells from human Wilms’ tumour xenografts unveils new therapeutic targets. EMBO Mol Med. 2013;5(1):18–37.

    Article  CAS  PubMed  Google Scholar 

  116. Shukrun R, Pode-Shakked N, Pleniceanu O, Omer D, Vax E, Peer E, et al. Wilms’ tumor blastemal stem cells dedifferentiate to propagate the tumor bulk. Stem Cell Reports. 2014;3(1):24–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Raved D, Tokatly-Latzer I, Anafi L, Harari-Steinberg O, Barshack I, Dekel B, et al. Blastemal NCAM(+)ALDH(+) Wilms’ tumor cancer stem cells correlate with disease progression and poor clinical outcome: a pilot study. to propagate the tumor bulk. Pathol Res Pract. 2019;215(8):152491.

    Article  CAS  PubMed  Google Scholar 

  118. Musah S, Mammoto A, Ferrante TC, Jeanty SSF, Hirano-Kobayashi M, Mammoto T, et al. Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip. Nat Biomed Eng. 2017;1:0069.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat Med. 2013;19:646–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Homan KA, Kolesky DB, Skylar-Scott MA, Herrmann J, Obuobi H, Moisan A, et al. Bioprinting of 3D convoluted renal proximal tubules on perfusable chips. Sci Rep. 2016;6:34845.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. Peter Karagiannis, CiRA, Kyoto University, for critically reading and revising this manuscript. The research of K.O. is supported by the Japan Agency for Medical Research and Development (AMED) through its research grant “Core Center for iPS Cell Research, Technological Development and The Acceleration Program for Intractable Diseases Research utilizing Disease-specific iPS cells, Research Center Network for Realization of Regenerative Medicine” and “Research Project for Practical Applications of Regenerative Medicine” and by the Japan Society for the Promotion of Science (JSPS) through Grants-in-Aid for Scientific Research (B) 18H02826. The research of B.D. is supported by the Lisa and David Pulver Family Foundation, the Pearl and Dr. (MD) Yechezkiel Klayman Chair of Urology (Tel Aviv University), the Israel Science Foundation (ISF, grant No. 2071/17), the Israel Science Foundation (ISF, grant No. 1814/20), Israel Innovation authority KAMIN (grant No. 61910), Ministry of Science and Technology (grant No. 3-16220) – USA, Israel Binational Science Foundation (BSF, grant No. 2017274), and by the Euro-Asian Jewish Congress.

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Authors and Affiliations

  1. Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan

    Kenji Osafune

  2. The Pediatric Stem Cell Research Institute and Pediatric Nephrology Division, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Oren Pleniceanu & Benjamin Dekel

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  1. Kenji Osafune
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  2. Oren Pleniceanu
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  3. Benjamin Dekel
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Correspondence to Kenji Osafune .

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Editors and Affiliations

  1. Division of Nephrology, Bambino Gesù Children’s Hospital –, ROMA, Roma, Italy

    Francesco Emma

  2. Division of Nephrology and Hypertension The Heart Institute, University of Cincinnati Cincinnati Children’s Hospital Medical C, Cincinnati, OH, USA

    Stuart Goldstein

  3. Division of Nephrology, All India Institute of Medical Sciences, Ansari Nagar East, Delhi, India

    Arvind Bagga

  4. Division of Pediatric Nephrology, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA

    Carlton M. Bates

  5. Renal Unit, Graet Ormond Street Hospital, London, UK

    Rukshana Shroff

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Osafune, K., Pleniceanu, O., Dekel, B. (2021). Stem Cells and Kidney Regeneration. In: Emma, F., Goldstein, S., Bagga, A., Bates, C.M., Shroff, R. (eds) Pediatric Nephrology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27843-3_16-2

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  • DOI: https://doi.org/10.1007/978-3-642-27843-3_16-2

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  • Print ISBN: 978-3-642-27843-3

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  1. Latest

    Stem Cells and Kidney Regeneration
    Published:
    08 June 2021

    DOI: https://doi.org/10.1007/978-3-642-27843-3_16-2

  2. Original

    Translational Research Methods: Renal Stem Cells
    Published:
    25 February 2015

    DOI: https://doi.org/10.1007/978-3-642-27843-3_16-1

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