Regeneration of glomerular podocytes by human renal progenitors.
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.
Ronconi
Elisa
E
Excellence Center for Research, Transfer and High Education Denothe, University of Florence, 50139, Firenze, Italy.
Sagrinati
Costanza
C
Angelotti
Maria Lucia
ML
Lazzeri
Elena
E
Mazzinghi
Benedetta
B
Ballerini
Lara
L
Parente
Eliana
E
Becherucci
Francesca
F
Gacci
Mauro
M
Carini
Marco
M
Maggi
Enrico
E
Serio
Mario
M
Vannelli
Gabriella Barbara
GB
Lasagni
Laura
L
Romagnani
Sergio
S
Romagnani
Paola
P
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D050476:Bowman Capsule / Q000378:metabolism; D051927:CD24 Antigen / Q000096:biosynthesis; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007668:Kidney / Q000166:cytology* / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D010455:Peptides; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D011507:Proteinuria / Q000378:metabolism; D012038:Regeneration; D013234:Stem Cells
D000071916:AC133 Antigen; D015703:Antigens, CD; D051927:CD24 Antigen; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse