Skip to main content

Advertisement

Log in

Label-retaining cells in the kidney: origin of regenerating cells after renal ischemia

  • REVIEW ARTICLE
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

The kidney is capable of regeneration. In response to a variety of insults, renal epithelial tubular cells dedifferentiate into an immature phenotype, proliferate, migrate to the injured area, and redifferentiate into mature polarized epithelial cells. In animal models of acute kidney injury induced by renal ischemia or renal toxins, various growth factors, transcription factors, chemokines, and extracellular matrix components have been demonstrated to be involved in the regeneration process. Recent research has suggested the existence of renal stem/progenitor cells in the kidney and their involvement in renal regeneration. In this review, we will focus on the mechanisms of tubular regeneration after kidney injury, particularly on label-retaining cells actively engaged in this process, and discuss their potential as targets of regenerative therapy for various kidney diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. RC Harris EG Neilson (2006) ArticleTitleToward a unified theory of renal progression Annu Rev Med 57 365–80 Occurrence Handle1:CAS:528:DC%2BD28Xis1CksLY%3D Occurrence Handle10.1146/annurev.med.57.121304.131342 Occurrence Handle16409155

    Article  CAS  PubMed  Google Scholar 

  2. LG Cantley (2005) ArticleTitleAdult stem cells in the repair of the injured renal tubule Nat Clin Pract Nephrol 1 22–32 Occurrence Handle1:CAS:528:DC%2BD28XhvVSrsrg%3D Occurrence Handle10.1038/ncpneph0021 Occurrence Handle16932361

    Article  CAS  PubMed  Google Scholar 

  3. C van Kooten MR Daha LA Van Es (1999) ArticleTitleTubular epithelial cells: a critical cell type in the regulation of renal inflammatory processes Exp Nephrol 7 429–37 Occurrence Handle1:CAS:528:DyaK1MXnsFGlu7c%3D Occurrence Handle10.1159/000020622 Occurrence Handle10559641

    Article  CAS  PubMed  Google Scholar 

  4. JV Bonventre (2003) ArticleTitleDedifferentiation and proliferation of surviving epithelial cells in acute renal failure J Am Soc Nephrol 14 IssueIDSuppl 1 S55–61 Occurrence Handle10.1097/01.ASN.0000067652.51441.21 Occurrence Handle12761240

    Article  PubMed  Google Scholar 

  5. S Nigam W Lieberthal (2000) ArticleTitleAcute renal failure. III. The role of growth factors in the process of renal regeneration and repair Am J Physiol Renal Physiol 279 F3–F11 Occurrence Handle1:CAS:528:DC%2BD3cXltlyqtrk%3D Occurrence Handle10.1152/ajprenal.2000.279.1.F3 Occurrence Handle10894783

    Article  CAS  PubMed  Google Scholar 

  6. B Lelongt P Ronco (2003) ArticleTitleRole of extracellular matrix in kidney development and repair Pediatr Nephrol 18 731–42 Occurrence Handle10.1007/s00467-003-1153-x Occurrence Handle12811645

    Article  PubMed  Google Scholar 

  7. MM Shah RV Sampogna H Sakurai KT Bush SK Nigam (2004) ArticleTitleBranching morphogenesis and kidney disease Development 131 1449–62 Occurrence Handle1:CAS:528:DC%2BD2cXjsFKltLc%3D Occurrence Handle10.1242/dev.01089 Occurrence Handle15023929

    Article  CAS  PubMed  Google Scholar 

  8. A Maeshima Y Nojima I Kojima (2001) ArticleTitleThe role of the activin-follistatin system in the developmental and regeneration processes of the kidney Cytokine Growth Factor Rev 12 289–98 Occurrence Handle1:CAS:528:DC%2BD3MXmsFCht7c%3D Occurrence Handle10.1016/S1359-6101(01)00010-7 Occurrence Handle11544099

    Article  CAS  PubMed  Google Scholar 

  9. A Maeshima YQ Zhang Y Nojima T Naruse I Kojima (2001) ArticleTitleInvolvement of the activin-follistatin system in tubular regeneration after renal ischemia in rats J Am Soc Nephrol 12 1685–95 Occurrence Handle1:CAS:528:DC%2BD3MXlvVCku7s%3D Occurrence Handle11461941

    CAS  PubMed  Google Scholar 

  10. A Maeshima Y Nojima I Kojima (2002) ArticleTitleActivin A: an autocrine regulator of cell growth and differentiation in renal proximal tubular cells Kidney Int 62 446–54 Occurrence Handle1:CAS:528:DC%2BD38Xmt1Glsrk%3D Occurrence Handle10.1046/j.1523-1755.2002.00463.x Occurrence Handle12110005

    Article  CAS  PubMed  Google Scholar 

  11. A Maeshima K Maeshima Y Nojima I Kojima (2002) ArticleTitleInvolvement of Pax-2 in the action of activin A on tubular cell regeneration J Am Soc Nephrol 13 2850–9 Occurrence Handle1:CAS:528:DC%2BD38XoslSnt74%3D Occurrence Handle10.1097/01.ASN.0000035086.93977.E9 Occurrence Handle12444203

    Article  CAS  PubMed  Google Scholar 

  12. A Maeshima DA Vaughn Y Choi SK Nigam (2006) ArticleTitleActivin A is an endogenous inhibitor of ureteric bud outgrowth from the Wolffian duct Dev Biol 295 473–85 Occurrence Handle1:CAS:528:DC%2BD28Xmt1yns78%3D Occurrence Handle10.1016/j.ydbio.2006.03.011 Occurrence Handle16643884

    Article  CAS  PubMed  Google Scholar 

  13. A Maeshima S Yamashita K Maeshima I Kojima Y Nojima (2003) ArticleTitleActivin A produced by ureteric bud is a differentiation factor for metanephric mesenchyme J Am Soc Nephrol 14 1523–34 Occurrence Handle1:CAS:528:DC%2BD3sXjslantbs%3D Occurrence Handle10.1097/01.ASN.0000067419.86611.21 Occurrence Handle12761253

    Article  CAS  PubMed  Google Scholar 

  14. KT Bush H Sakurai DL Steer MO Leonard RV Sampogna TN Meyer et al. (2004) ArticleTitleTGF-beta superfamily members modulate growth, branching, shaping, and patterning of the ureteric bud Dev Biol 266 285–98 Occurrence Handle1:CAS:528:DC%2BD2cXltF2rtA%3D%3D Occurrence Handle10.1016/j.ydbio.2003.10.023 Occurrence Handle14738877

    Article  CAS  PubMed  Google Scholar 

  15. A Maeshima S Shiozaki T Tajima Y Nakazato T Naruse I Kojima (2000) ArticleTitleNumber of glomeruli is increased in the kidney of transgenic mice expressing the truncated type II activin receptor Biochem Biophys Res Commun 268 445–9 Occurrence Handle1:CAS:528:DC%2BD3cXhtFGjtLc%3D Occurrence Handle10.1006/bbrc.2000.2171 Occurrence Handle10679224

    Article  CAS  PubMed  Google Scholar 

  16. A Maeshima YQ Zhang M Furukawa T Naruse I Kojima (2000) ArticleTitleHepatocyte growth factor induces branching tubulogenesis in MDCK cells by modulating the activin-follistatin system Kidney Int 58 1511–22 Occurrence Handle1:CAS:528:DC%2BD3cXntlyltbw%3D Occurrence Handle10.1046/j.1523-1755.2000.00313.x Occurrence Handle11012886

    Article  CAS  PubMed  Google Scholar 

  17. GR Dressler (2006) ArticleTitleThe cellular basis of kidney development Annu Rev Cell Dev Biol 22 509–29 Occurrence Handle1:CAS:528:DC%2BD28Xht1yjs7jL Occurrence Handle10.1146/annurev.cellbio.22.010305.104340 Occurrence Handle16822174

    Article  CAS  PubMed  Google Scholar 

  18. MR Alison R Poulsom S Forbes NA Wright (2002) ArticleTitleAn introduction to stem cells J Pathol 197 419–23 Occurrence Handle10.1002/path.1187 Occurrence Handle12115858

    Article  PubMed  Google Scholar 

  19. G Cotsarelis TT Sun RM Lavker (1990) ArticleTitleLabel-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis Cell 61 1329–37 Occurrence Handle1:STN:280:DyaK3czgsVyqsw%3D%3D Occurrence Handle10.1016/0092-8674(90)90696-C Occurrence Handle2364430

    Article  CAS  PubMed  Google Scholar 

  20. G Cotsarelis SZ Cheng G Dong TT Sun RM Lavker (1989) ArticleTitleExistence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells Cell 57 201–9 Occurrence Handle1:STN:280:DyaL1M7psFagsw%3D%3D Occurrence Handle10.1016/0092-8674(89)90958-6 Occurrence Handle2702690

    Article  CAS  PubMed  Google Scholar 

  21. KU Hong SD Reynolds A Giangreco CM Hurley BR Stripp (2001) ArticleTitleClara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion Am J Respir Cell Mol Biol 24 671–81 Occurrence Handle1:CAS:528:DC%2BD3MXltVWhsbo%3D Occurrence Handle10.1165/ajrcmb.24.6.4498 Occurrence Handle11415931

    Article  CAS  PubMed  Google Scholar 

  22. DW Borthwick M Shahbazian QT Krantz JR Dorin SH Randell (2001) ArticleTitleEvidence for stem-cell niches in the tracheal epithelium Am J Respir Cell Mol Biol 24 662–70 Occurrence Handle1:CAS:528:DC%2BD3MXltVWhsb0%3D Occurrence Handle10.1165/ajrcmb.24.6.4217 Occurrence Handle11415930

    Article  CAS  PubMed  Google Scholar 

  23. B Duvillie M Attali V Aiello E Quemeneur R Scharfmann (2003) ArticleTitleLabel-retaining cells in the rat pancreas: location and differentiation potential in vitro Diabetes 52 2035–42 Occurrence Handle1:CAS:528:DC%2BD3sXlvFCgtL8%3D Occurrence Handle10.2337/diabetes.52.8.2035 Occurrence Handle12882920

    Article  CAS  PubMed  Google Scholar 

  24. W Chen K Hara Q Tian K Zhao T Yoshitomi (2007) ArticleTitleExistence of small slow-cycling Langerhans cells in the limbal basal epithelium that express ABCG2 Exp Eye Res 84 626–34 Occurrence Handle1:CAS:528:DC%2BD2sXjtFGku7c%3D Occurrence Handle10.1016/j.exer.2006.11.006 Occurrence Handle17254566

    Article  CAS  PubMed  Google Scholar 

  25. ZG Wei G Cotsarelis TT Sun RM Lavker (1995) ArticleTitleLabel-retaining cells are preferentially located in fornical epithelium: implications on conjunctival epithelial homeostasis Invest Ophthalmol Vis Sci 36 236–46 Occurrence Handle1:STN:280:DyaK2M7it1ehsA%3D%3D Occurrence Handle7822151

    CAS  PubMed  Google Scholar 

  26. S Claudinot M Nicolas H Oshima A Rochat Y Barrandon (2005) ArticleTitleLong-term renewal of hair follicles from clonogenic multipotent stem cells Proc Natl Acad Sci U S A 102 14677–82 Occurrence Handle1:CAS:528:DC%2BD2MXhtFKjsb7I Occurrence Handle10.1073/pnas.0507250102 Occurrence Handle16203973 Occurrence Handle1253596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. M Ohyama A Terunuma CL Tock MF Radonovich CA Pise-Masison SB Hopping et al. (2006) ArticleTitleCharacterization and isolation of stem cell-enriched human hair follicle bulge cells J Clin Invest 116 249–60 Occurrence Handle1:CAS:528:DC%2BD28XjslOgtw%3D%3D Occurrence Handle10.1172/JCI26043 Occurrence Handle16395407 Occurrence Handle1323261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. K Urbanek D Cesselli M Rota A Nascimbene A De Angelis T Hosoda et al. (2006) ArticleTitleStem cell niches in the adult mouse heart Proc Natl Acad Sci U S A 103 9226–31 Occurrence Handle1:CAS:528:DC%2BD28XmsVWjtrg%3D Occurrence Handle10.1073/pnas.0600635103 Occurrence Handle16754876 Occurrence Handle1474010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. T Tumbar G Guasch V Greco C Blanpain WE Lowry M Rendl E Fuchs (2004) ArticleTitleDefining the epithelial stem cell niche in skin Science 303 359–63 Occurrence Handle1:CAS:528:DC%2BD2cXjtFGmsg%3D%3D Occurrence Handle10.1126/science.1092436 Occurrence Handle14671312

    Article  CAS  PubMed  Google Scholar 

  30. RL Waikel Y Kawachi PA Waikel XJ Wang DR Roop (2001) ArticleTitleDeregulated expression of c-Myc depletes epidermal stem cells Nat Genet 28 165–8 Occurrence Handle1:CAS:528:DC%2BD3MXktFOrtLc%3D Occurrence Handle10.1038/88889 Occurrence Handle11381265

    Article  CAS  PubMed  Google Scholar 

  31. H Tani RJ Morris P Kaur (2000) ArticleTitleEnrichment for murine keratinocyte stem cells based on cell surface phenotype Proc Natl Acad Sci U S A 97 10960–5 Occurrence Handle1:CAS:528:DC%2BD3cXnt1ahsb8%3D Occurrence Handle10.1073/pnas.97.20.10960 Occurrence Handle11005869 Occurrence Handle27131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. HB Zhang CP Ren XY Yang L Wang H Li M Zhao et al. (2007) ArticleTitleIdentification of label-retaining cells in nasopharyngeal epithelia and nasopharyngeal carcinoma tissues Histochem Cell Biol 127 347–54 Occurrence Handle1:CAS:528:DC%2BD2sXhsFCgsro%3D Occurrence Handle10.1007/s00418-006-0251-9 Occurrence Handle17139514

    Article  CAS  PubMed  Google Scholar 

  33. T Togo A Utani M Naitoh M Ohta Y Tsuji N Morikawa et al. (2006) ArticleTitleIdentification of cartilage progenitor cells in the adult ear perichondrium: utilization for cartilage reconstruction Lab Invest 86 445–57 Occurrence Handle1:CAS:528:DC%2BD28Xjs1agtLk%3D Occurrence Handle10.1038/labinvest.3700409 Occurrence Handle16625212

    Article  CAS  PubMed  Google Scholar 

  34. D Croagh WA Phillips R Redvers RJ Thomas P Kaur (2007) ArticleTitleIdentification of candidate murine esophageal stem cells using a combination of cell kinetic studies and cell surface markers Stem Cells 25 313–8 Occurrence Handle1:CAS:528:DC%2BD2sXivVOltr8%3D Occurrence Handle10.1634/stemcells.2006-0421 Occurrence Handle17038667

    Article  CAS  PubMed  Google Scholar 

  35. RW Chan CE Gargett (2006) ArticleTitleIdentification of label-retaining cells in mouse endometrium Stem Cells 24 1529–38 Occurrence Handle1:CAS:528:DC%2BD28XhtFKlsbfO Occurrence Handle10.1634/stemcells.2005-0411 Occurrence Handle16456137

    Article  CAS  PubMed  Google Scholar 

  36. GH Smith (2005) ArticleTitleLabel-retaining epithelial cells in mouse mammary gland divide asymmetrically and retain their template DNA strands Development 132 681–7 Occurrence Handle1:CAS:528:DC%2BD2MXit12gtL0%3D Occurrence Handle10.1242/dev.01609 Occurrence Handle15647322

    Article  CAS  PubMed  Google Scholar 

  37. V Shinin B Gayraud-Morel D Gomes S Tajbakhsh (2006) ArticleTitleAsymmetric division and cosegregation of template DNA strands in adult muscle satellite cells Nat Cell Biol 8 677–87 Occurrence Handle1:CAS:528:DC%2BD28XmsVentb4%3D Occurrence Handle10.1038/ncb1425 Occurrence Handle16799552

    Article  CAS  PubMed  Google Scholar 

  38. A Maeshima S Yamashita Y Nojima (2003) ArticleTitleIdentification of renal progenitor-like tubular cells that participate in the regeneration processes of the kidney J Am Soc Nephrol 14 3138–46 Occurrence Handle10.1097/01.ASN.0000098685.43700.28 Occurrence Handle14638912

    Article  PubMed  Google Scholar 

  39. JA Knoblich (2001) ArticleTitleAsymmetric cell division during animal development Nat Rev Mol Cell Biol 2 11–20 Occurrence Handle1:CAS:528:DC%2BD3MXivVWms7w%3D Occurrence Handle10.1038/35048085 Occurrence Handle11413461

    Article  CAS  PubMed  Google Scholar 

  40. JR Merok JA Lansita JR Tunstead JL Sherley (2002) ArticleTitleCosegregation of chromosomes containing immortal DNA strands in cells that cycle with asymmetric stem cell kinetics Cancer Res 62 6791–5 Occurrence Handle1:CAS:528:DC%2BD38XpsVahsrw%3D Occurrence Handle12460886

    CAS  PubMed  Google Scholar 

  41. Y Fujigaki T Goto M Sakakima H Fukasawa T Miyaji T Yamamoto A Hishida (2006) ArticleTitleKinetics and characterization of initially regenerating proximal tubules in S3 segment in response to various degrees of acute tubular injury Nephrol Dial Transplant 21 41–50 Occurrence Handle1:CAS:528:DC%2BD28XisFKisw%3D%3D Occurrence Handle10.1093/ndt/gfi035 Occurrence Handle16077144

    Article  CAS  PubMed  Google Scholar 

  42. JA Oliver O Maarouf FH Cheema TP Martens Q Al-Awqati (2004) ArticleTitleThe renal papilla is a niche for adult kidney stem cells J Clin Invest 114 795–804 Occurrence Handle1:CAS:528:DC%2BD2cXnslWiurs%3D Occurrence Handle10.1172/JCI20921 Occurrence Handle15372103 Occurrence Handle516259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. A Vogetseder A Karadeniz B Kaissling M Le Hir (2005) ArticleTitleTubular cell proliferation in the healthy rat kidney Histochem Cell Biol 124 97–104 Occurrence Handle1:CAS:528:DC%2BD2MXhtV2kt7%2FM Occurrence Handle10.1007/s00418-005-0023-y Occurrence Handle16133123

    Article  CAS  PubMed  Google Scholar 

  44. EG Neilson (2006) ArticleTitleMechanisms of disease: Fibroblasts – a new look at an old problem Nat Clin Pract Nephrol 2 101–8 Occurrence Handle1:CAS:528:DC%2BD28XmvV2ntL4%3D Occurrence Handle10.1038/ncpneph0093 Occurrence Handle16932401

    Article  CAS  PubMed  Google Scholar 

  45. S Yamashita A Maeshima Y Nojima (2005) ArticleTitleInvolvement of renal progenitor tubular cells in epithelial-to-mesenchymal transition in fibrotic rat kidneys J Am Soc Nephrol 16 2044–51 Occurrence Handle1:CAS:528:DC%2BD2MXms1egs78%3D Occurrence Handle10.1681/ASN.2004080681 Occurrence Handle15888566

    Article  CAS  PubMed  Google Scholar 

  46. PE Mozdziak PM Pulvermacher E Schultz K Schell (2000) ArticleTitleHoechst fluorescence intensity can be used to separate viable bromodeoxyuridine-labeled cells from viable non-bromodeoxyuridine-labeled cells Cytometry 41 89–95 Occurrence Handle1:STN:280:DC%2BD3M7htlShsA%3D%3D Occurrence Handle10.1002/1097-0320(20001001)41:2<89::AID-CYTO2>3.0.CO;2-I Occurrence Handle11002263

    Article  CAS  PubMed  Google Scholar 

  47. A Maeshima H Sakurai SK Nigam (2006) ArticleTitleAdult kidney tubular cell population showing phenotypic plasticity, tubulogenic capacity, and integration capability into developing kidney J Am Soc Nephrol 17 188–98 Occurrence Handle1:CAS:528:DC%2BD28XhtFyqu7g%3D Occurrence Handle10.1681/ASN.2005040370 Occurrence Handle16338966

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Akito Maeshima.

About this article

Cite this article

Maeshima, A. Label-retaining cells in the kidney: origin of regenerating cells after renal ischemia. Clin Exp Nephrol 11, 269–274 (2007). https://doi.org/10.1007/s10157-007-0500-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-007-0500-9

Key words

Navigation