Regeneration of glomerular podocytes by human renal progenitors

J Am Soc Nephrol. 2009 Feb;20(2):322-32. doi: 10.1681/ASN.2008070709. Epub 2008 Dec 17.

Abstract

Depletion of podocytes, common to glomerular diseases in general, plays a role in the pathogenesis of glomerulosclerosis. Whether podocyte injury in adulthood can be repaired has not been established. Here, we demonstrate that in the adult human kidney, CD133+CD24+ cells consist of a hierarchical population of progenitors that are arranged in a precise sequence within Bowman's capsule and exhibit heterogeneous potential for differentiation and regeneration. Cells localized to the urinary pole that expressed CD133 and CD24, but not podocyte markers (CD133+CD24+PDX- cells), could regenerate both tubular cells and podocytes. In contrast, cells localized between the urinary pole and vascular pole that expressed both progenitor and podocytes markers (CD133+CD24+PDX+) could regenerate only podocytes. Finally, cells localized to the vascular pole did not exhibit progenitor markers, but displayed phenotypic features of differentiated podocytes (CD133-CD24-PDX+ cells). Injection of CD133+CD24+PDX- cells, but not CD133+CD24+PDX+ or CD133-CD24- cells, into mice with adriamycin-induced nephropathy reduced proteinuria and improved chronic glomerular damage, suggesting that CD133+CD24+PDX- cells could potentially treat glomerular disorders characterized by podocyte injury, proteinuria, and progressive glomerulosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Animals
  • Antigens, CD / biosynthesis
  • Bowman Capsule / metabolism
  • CD24 Antigen / biosynthesis
  • Female
  • Glomerulosclerosis, Focal Segmental / metabolism
  • Glycoproteins / biosynthesis
  • Humans
  • Kidney / cytology*
  • Kidney / metabolism
  • Kidney Glomerulus / metabolism*
  • Kidney Glomerulus / pathology
  • Mice
  • Mice, SCID
  • Peptides
  • Podocytes / metabolism*
  • Podocytes / pathology
  • Proteinuria / metabolism
  • Regeneration*
  • Stem Cells

Substances

  • AC133 Antigen
  • Antigens, CD
  • CD24 Antigen
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse