title: 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.affiliation: Excellence Center for Research, Transfer and High Education Denothe, University of Florence, 50139, Firenze, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Ronconi
authors.forename: Costanza
authors.initials: C
authors.lastname: Sagrinati
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Angelotti
authors.forename: Elena
authors.initials: E
authors.lastname: Lazzeri
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mazzinghi
authors.forename: Lara
authors.initials: L
authors.lastname: Ballerini
authors.forename: Eliana
authors.initials: E
authors.lastname: Parente
authors.forename: Francesca
authors.initials: F
authors.lastname: Becherucci
authors.forename: Mauro
authors.initials: M
authors.lastname: Gacci
authors.forename: Marco
authors.initials: M
authors.lastname: Carini
authors.forename: Enrico
authors.initials: E
authors.lastname: Maggi
authors.forename: Mario
authors.initials: M
authors.lastname: Serio
authors.forename: Gabriella Barbara
authors.initials: GB
authors.lastname: Vannelli
authors.forename: Laura
authors.initials: L
authors.lastname: Lasagni
authors.forename: Sergio
authors.initials: S
authors.lastname: Romagnani
authors.forename: Paola
authors.initials: P
authors.lastname: Romagnani
mesh_terms: 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
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D051927:CD24 Antigen; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse