Cystogenic potential of CD133+ progenitor cells of human polycystic kidneys

J Pathol. 2011 Sep;225(1):129-41. doi: 10.1002/path.2920. Epub 2011 Jun 27.


In autosomal dominant polycystic kidney disease, cysts arise focally and disrupt normal renal tissue leading to renal failure. In the present study, we show that cyst-lining cells express the stem cell marker CD133. CD133+ progenitor cells isolated from polycystic kidney, carrying mutations of PKD genes, showed a dedifferentiated phenotype similar to CD133+ progenitor cells from normal kidney. However, these cells were more proliferative and presented a defective epithelial differentiation phenotype with respect to normal renal CD133+ cells as they were not able to express all tubular epithelial cell markers when cultured in epithelial differentiation medium. Polycystic CD133+ cells, in contrast to normal renal CD133+ cells, formed cysts in vitro in a three-dimensional culture system and in vivo when injected subcutaneously within Matrigel in SCID mice. Rapamycin treatment reduced in vitro proliferation of polycystic CD133+ cells and decreased cystogenesis both in vitro and in vivo. The in vitro epithelial differentiation was only partially improved by rapamycin. These results indicate that polycystic CD133+ cells retain a dedifferentiated phenotype and the ability to generate cysts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Animals
  • Antigens, CD / metabolism*
  • Apoptosis / drug effects
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Glycoproteins / metabolism*
  • Humans
  • Kidney / metabolism
  • Mice
  • Mice, SCID
  • Mutation, Missense
  • Peptides / metabolism*
  • Polycystic Kidney, Autosomal Dominant / genetics
  • Polycystic Kidney, Autosomal Dominant / metabolism*
  • Sirolimus / pharmacology
  • Stem Cells / metabolism*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TRPP Cation Channels / genetics
  • Transplantation, Heterologous


  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus