Regeneration of glomerular podocytes by human renal progenitors.

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.

• Authors: Elisa Ronconi, Costanza Sagrinati, Maria Lucia Angelotti, Elena Lazzeri, Benedetta Mazzinghi, Lara Ballerini, Eliana Parente, Francesca Becherucci, Mauro Gacci, Marco Carini, Enrico Maggi, Mario Serio, Gabriella Barbara Vannelli, Laura Lasagni, Sergio Romagnani, Paola Romagnani
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 20 Issue 2 Pg. 322-32 (Feb 2009) ISSN: 1533-3450 [Electronic] United States
• PMID: 19092120 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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