Regenerative potential of embryonic renal multipotent progenitors in acute renal failure.
Bone marrow-and adult kidney-derived stem/progenitor cells hold promise in the development of therapies for renal failure. Here is reported the identification and characterization of renal multipotent progenitors in human embryonic kidneys that share CD24 and CD133 surface expression with adult renal progenitors and have the capacity for self-renewal and multilineage differentiation. It was found that these CD24+CD133+ cells constitute the early primordial nephron but progressively disappear during nephron development until they become selectively localized to the urinary pole of Bowman's capsule. When isolated and injected into SCID mice with acute renal failure from glycerol-induced rhabdomyolysis, these cells regenerated different portions of the nephron, reduced tissue necrosis and fibrosis, and significantly improved renal function. No tumorigenic potential was observed. It is concluded that CD24+CD133+ cells represent a subset of multipotent embryonic progenitors that persist in human kidneys from early stages of nephrogenesis. The ability of these cells to repair renal damage, together with their apparent lack of tumorigenicity, suggests their potential in the treatment of renal failure.
Lazzeri
Elena
E
Excellence Center for Research, Transfer and High Education for the Development of DE NOVO THERAPIES, University of Florence, Florence, Italy.
Crescioli
Clara
C
Ronconi
Elisa
E
Mazzinghi
Benedetta
B
Sagrinati
Costanza
C
Netti
Giuseppe Stefano
GS
Angelotti
Maria Lucia
ML
Parente
Eliana
E
Ballerini
Lara
L
Cosmi
Lorenzo
L
Maggi
Laura
L
Gesualdo
Loreto
L
Rotondi
Mario
M
Annunziato
Francesco
F
Maggi
Enrico
E
Lasagni
Laura
L
Serio
Mario
M
Romagnani
Sergio
S
Vannelli
Gabriella Barbara
GB
Romagnani
Paola
P
D000071916:AC133 Antigen; D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D051927:CD24 Antigen / Q000096:biosynthesis; D004622:Embryo, Mammalian / Q000166:cytology*; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D018613:Microscopy, Confocal; D009399:Nephrons / Q000473:pathology; D010455:Peptides; D012038:Regeneration; D051437:Renal Insufficiency / Q000378:metabolism / Q000473:pathology*; D012206:Rhabdomyolysis / Q000473:pathology / Q000628:therapy; D013234:Stem Cells / Q000166:cytology*
D000071916:AC133 Antigen; D015703:Antigens, CD; D051927:CD24 Antigen; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse