Skip to main content
Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;8(4):474–487. doi: 10.1111/j.1582-4934.2004.tb00472.x

In search of adult renal stem cells

F Anglani 1,, M Forino 1, D Del Prete 1, E Tosetto 1, R Torregrossa 1, A D'Angelo 1
PMCID: PMC6740109  PMID: 15601576

Abstract

The therapeutic potential of adult stem cells in the treatment of chronic degenerative diseases has becoming increasingly evident over the last few years. Significant attention is currently being paid to the development of novel treatments for acute and chronic kidney diseases too. To date, promising sources of stem cells for renal therapies include adult bone marrow stem cells and the kidney precursors present in the early embryo. Both cells have clearly demonstrated their ability to differentiate into the kidney's specialized structures. Adult renal stem cells have yet to be identified, but the papilla is where the stem cell niche is probably located. Now we need to isolate and characterize the fraction of papillary cells that constitute the putative renal stem cells. Our growing understanding of the cellular and molecular mechanisms behind kidney regeneration and repair processes ‐ together with a knowledge of the embryonic origin of renal cells ‐ should induce us, however, to bear in mind that in the kidney, as in other mesenchymal tissues, the need for a real stem cell compartment might be less important than the phenotypic flexibility of tubular cells. Thus, by displaying their plasticity during kidney maintenance and repair, terminally differentiated cells may well function as multipotent stem cells despite being at a later stage of maturation than adult stem cells. One of the major tasks of Regenerative Medicine will be to disclose the molecular mechanisms underlying renal tubular plasticity and to exploit its biological and therapeutic potential.

Keywords: renal stem cells, transdifferentiation, regeneration

References

  • 1. Labat M.L., Stem cells and the promise of eternal youth: embryonic versus adult stem cells, Biomed. Pharmacother., 55: 179–185, 2001. [DOI] [PubMed] [Google Scholar]
  • 2. Alison M.R., Poulsom R., Forbes S., Wright N.A., An introduction to stem cells, J. Pathol., 197: 419–423, 2002. [DOI] [PubMed] [Google Scholar]
  • 3. Pappenheim A., Prinzipien der neuren morphologischen Haematozytologie nach zytogenetischer Grundlage, Folia Haematologica, 21: 91, 1917. [Google Scholar]
  • 4. Till J.E., McCulloch E.A., A direct measurement of the radiation sensitivity of normal mouse bone marrow cells, Radiat. Res., 19: 213–222, 1961. [PubMed] [Google Scholar]
  • 5. Potten C.S., Loeffler M., Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt, Development, 110: 1001–1020, 1990. [DOI] [PubMed] [Google Scholar]
  • 6. Galli R., Gritti A., Bonfanti L., Vescovi A.L., Neural stem cells: an overview, Circ. Res., 92: 598–608, 2003. [DOI] [PubMed] [Google Scholar]
  • 7. Shih C.C., Weng Y., Mamelak A., LeBon T., Hu M.C., Forman S.J., Identification of a candidate human neurohematopoietic stem‐cell population. Blood, 98: 2412–2422, 2001. [DOI] [PubMed] [Google Scholar]
  • 8. Galli L., Borello U., Gritti A., et al., Skeletal myogenic potential of human and mouse neural stem cells, Nat. Neurosci., 3: 986–991, 2000. [DOI] [PubMed] [Google Scholar]
  • 9. Clarke D.L., Johansson C.B., Wilbertz J., Veress B., Nilsson E., Karlstrom H., Lendahl U., Frisen J., Generalized potential of adult neural stem cells, Science, 288: 1660–1663, 2000. [DOI] [PubMed] [Google Scholar]
  • 10. Shefer G., Wleklinski‐Lee M., Yablonka‐Reuveni Z., Skeletal muscle satellite cells can spontaneously enter an alternative mesenchymal pathway. J. Cell Sci., 117: 5393–5404, 2004. [DOI] [PubMed] [Google Scholar]
  • 11. Williams J.T., Southerland S.S., Souza J., et al., Cells isolated from adult human skeletal muscle capable of differentiating into multiple mesodermal phenotypes, Am. Surg., 65: 22–26, 1999. [PubMed] [Google Scholar]
  • 12. Sell S., Electron microscopic identification of putative liver stem cells and intermediate hepatocytes following periportal necrosis induced in rats by allyl alcohol, Stem Cells, 5: 378–385, 1997. [DOI] [PubMed] [Google Scholar]
  • 13. Roskams T.A., Libbrecht L., Desmet V.J., Progenitor cells in diseased human liver, Semin. Liver Dis., 23: 385–396, 2003. [DOI] [PubMed] [Google Scholar]
  • 14. Fausto N., Campbell J.S., The role of hepatocytes and oval cells in liver regeneration and repopulation, Mech. Dev., 120: 117–130, 2003. [DOI] [PubMed] [Google Scholar]
  • 15. Smith G.H., Chepko G., Mammary epithelial stem cells, Microsc. Res. Tech., 52: 190–203, 2001. [DOI] [PubMed] [Google Scholar]
  • 16. Boecker W., Buerger H., Evidence of progenitor cells of glandular and myoepithelial cell lineages in the human adult female breast epithelium: a new progenitor (adult stem) cell concept, Cell Prolif., 36 Suppl 1: 73–84, 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Borthwick D.W., Shahbazian M., Kranzt Q.T., et al., Evidence for stem‐cell niches in the tracheal epithelium. Am J Respir Cell Mol Biol., 24: 662–670, 2001. [DOI] [PubMed] [Google Scholar]
  • 18. Ferrari G, Angelis Cusella‐De, Coletta M, et al. Muscle regeneration by bone‐marrow derived myogenic progenitor. Science 279: 1528–1530, 1998. [DOI] [PubMed] [Google Scholar]
  • 19. Kanwar Y.S., Kumar A., Ota K., et al. Identification of developmentally regulated mesodermal‐ specific transcript in mouse embryonic metanephros, Am. J. Physiol. Renal Physiol. 282: F953–F965, 1998. [DOI] [PubMed] [Google Scholar]
  • 20. Horster M.F., Braun G.S., Huber S.M., Embryonic renal epithelia: induction, nephrogenesis, and cell differentiation. Physiol Rev., 79: 1157–1191, 1999. [DOI] [PubMed] [Google Scholar]
  • 21. Schedl A., Hastie N.D., Cross‐talk in kidney development. Curr. Opin. Genetics Dev., 10: 543–549, 2000. [DOI] [PubMed] [Google Scholar]
  • 22. Herzlinger D., Abramson R., Cohen D., Phenotypic conversion in renal development, J. Cell Sci. Suppl., 17: 61–64, 1993. [DOI] [PubMed] [Google Scholar]
  • 23. Qiao J., Cohen D., Herzlinger D., The metanephric blastema differentiates into collecting system and nephron epithelia in vitro , Development, 121: 3207–3214, 1995. [DOI] [PubMed] [Google Scholar]
  • 24. Al‐Awqati Q., Oliver J.A., Stem cells in the kidney, Kidney Int., 61: 387–395, 2002. [DOI] [PubMed] [Google Scholar]
  • 25. Dekel B., Reisner Y., Engraftment of human early kidney precursors, Transpl. Immunol., 12: 241–247, 2004. [DOI] [PubMed] [Google Scholar]
  • 26. Mendelsohn C., Batourina E., Fung S., et al., Stromal cells mediate retinoid‐dependent function essential for renal development. Development, 126: 1139–1148, 1999. [DOI] [PubMed] [Google Scholar]
  • 27. Levinson R., Mendelsohn C., Stromal progenitors are important for patterning epithelial and mesenchymal cell types in the embryonic kidney, Semin Cell Dev Biol. 14: 225–231, 2003. [DOI] [PubMed] [Google Scholar]
  • 28. Koller M.R., Manchel I., Palsson B., Importance of parenchymal: stromal cell ratio for the ex vivo reconstitution of human hematopoiesis. Stem Cells, 15: 305–313, 1997. [DOI] [PubMed] [Google Scholar]
  • 29. Oliver J.A., Maarouf O., Cheema F.H., Martens T.P., Al‐Awqati Q., The renal papilla is a niche for adult kidney stem cells. J. Clin. Invest., 114: 795–804, 2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. Alison M., Sarraf C., Hepatic stem cells. J. Hepatol., 29: 676–682, 1998. [DOI] [PubMed] [Google Scholar]
  • 31. Crosby H.A., Strain A.J., Adult liver stem cells: bone marrow, blood, or liver derived Gut. 48: 153–154, 2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Fausto N., Campbell J.S., The role of hepatocytes and oval cells in liver regeneration and repopulation, Mech Dev. 120: 117–130, 2003. [DOI] [PubMed] [Google Scholar]
  • 33. Matsumoto K., Nakamura T., Hepatocyte growth factor: renotropic role and potential therapeutics for renal diseases. Kidney Int., 59: 2023–2038, 2001. [DOI] [PubMed] [Google Scholar]
  • 34. Abbate M., Brown D., Bonventre J.V., Expression of NCAM recapitulates tubulogenic development in kidneys recovering fron acute ischemia. Am. J. Physiol. Renal. Physiol., 277: F454–F463, 1999. [DOI] [PubMed] [Google Scholar]
  • 35. Stahl P.J., Felsen D., Transforming growth factor beta, basement membrane, and epithelial‐mesenchymal transdifferentiation. Am. J. Pathol., 159: 1187–1192, 2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. Bianchi G., Muraglia A., Daga A., Corte G., et al., Microenvironment and stem properties of bone‐marrow derived mesenchymal cells, Wound Repair Regen., 9: 460–466, 2001. [DOI] [PubMed] [Google Scholar]
  • 37. Poulsom R., Forbes S., Hodivala‐Dilke K., et al., Bone marrow contributes to renal parenchymal turnover and regeneration, J. Pathol., 193: 1–7, 2001. [DOI] [PubMed] [Google Scholar]
  • 38. Grimm C.P., Nickerson P., Jeffery J., et al., Neointimal and tubulointerstitial infiltration by recipient mesenchymal cells in chronic renal‐allograft rejection, N. Engl. J. Med., 345: 93–97, 2001. [DOI] [PubMed] [Google Scholar]
  • 39. Ito T., Suzuki A., Imai E., Okabe M., Hori M., Bone marrow is a reservoir of repopulating mesangial cells during glomerular remodeling, J. Am. Soc. Nephrol., 12: 2625–2635, 2001. [DOI] [PubMed] [Google Scholar]
  • 40. Wulf G.G., Jackson K.A., Goodell M.A., Somatic stem cell plasticity: current evidence and emerging concepts, Exp. Hematol., 29: 1361–1370, 2001. [DOI] [PubMed] [Google Scholar]
  • 41. Takahashi T., Kalka C., Masuda H., et al., Ischemia and cytokine ‐induced mobilization of bone marrow‐derived endothelial progenitor cells for neovascularisation, Nat. Med., 5: 434–438, 1999. [DOI] [PubMed] [Google Scholar]
  • 42. Dreyfus P.A., Chretien F., Chazaud B., Kirova Y., Caramelle P., Garcia L., Butler‐Browne G., Gherardi R.K., Adult bone marrow‐derived stem cells in muscle connective tissue and satellite cell niches, Am J Pathol., 164: 773–779, 2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43. Kale S., Karihaloo A., Clark P.R., Kashgarian M., Krause D.S., Cantley L.G., Bone marrow stem cells contribute to repair of the ischemically injured renal tubule, J. Clin. Invest., 112: 42–49, 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44. Bianco P., Gehron Robey P., Marrow stromal stem cells. J. Clin. Invest., 105: 1663–1668, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45. Labat M.L., Milhaud G., Pouchelet M., Boireau P., On the track of a human circulating mesenchymal stem cell of neural crest origin. Biomed. Pharmacother., 54: 146–162, 2000. [DOI] [PubMed] [Google Scholar]
  • 46. Abe R., Donnelly S.C., Peng T., Bucala R., Metz C.N., Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J. Immunol., 166: 7556–7562, 2001. [DOI] [PubMed] [Google Scholar]
  • 47. Forbes S.J., Poulsom R., Wright N.A., Hepatic and renal differentiation from blood borne stem cells, Gene Ther., 9: 625–630, 2002. [DOI] [PubMed] [Google Scholar]
  • 48. Direkze N.C., Forbes S.J., Brittan M., Hunt T., Jeffery R., Preston S.L., Poulsom R., Hodivala‐Dilke K., Alison M.R., Wright N.A., Multiple organ engraftment by bonemarrow‐derived myofibroblasts and fibroblasts in bonemarrow‐transplanted mice. Stem Cells, 21: 514–520, 2003. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Cellular and Molecular Medicine are provided here courtesy of Blackwell Publishing

RESOURCES