Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys.
Regenerative medicine represents a critical clinical goal for patients with ESRD, but the identification of renal adult multipotent progenitor cells has remained elusive. It is demonstrated that in human adult kidneys, a subset of parietal epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem cell markers CD24 and CD133 and of the stem cell-specific transcription factors Oct-4 and BmI-1, in the absence of lineage-specific markers. This CD24+CD133+ PEC population, which could be purified from cultured capsulated glomeruli, revealed self-renewal potential and a high cloning efficiency. Under appropriate culture conditions, individual clones of CD24+CD133+ PEC could be induced to generate mature, functional, tubular cells with phenotypic features of proximal and/or distal tubules, osteogenic cells, adipocytes, and cells that exhibited phenotypic and functional features of neuronal cells. The injection of CD24+CD133+ PEC but not of CD24-CD133- renal cells into SCID mice that had acute renal failure resulted in the regeneration of tubular structures of different portions of the nephron. More important, treatment of acute renal failure with CD24+CD133+ PEC significantly ameliorated the morphologic and functional kidney damage. This study demonstrates the existence and provides the characterization of a population of resident multipotent progenitor cells in adult human glomeruli, potentially opening new avenues for the development of regenerative medicine in patients who have renal diseases.
Sagrinati
Costanza
C
Interdepartmental Laboratory of Cellular and Molecular Nephrology, University of Florence, Viale Pieraccini 6, 50139, Firenze, Italy.
Netti
Giuseppe Stefano
GS
Mazzinghi
Benedetta
B
Lazzeri
Elena
E
Liotta
Francesco
F
Frosali
Francesca
F
Ronconi
Elisa
E
Meini
Claudia
C
Gacci
Mauro
M
Squecco
Roberta
R
Carini
Marco
M
Gesualdo
Loreto
L
Francini
Fabio
F
Maggi
Enrico
E
Annunziato
Francesco
F
Lasagni
Laura
L
Serio
Mario
M
Romagnani
Sergio
S
Romagnani
Paola
P
D000071916:AC133 Antigen; D058186:Acute Kidney Injury / Q000503:physiopathology / Q000628:therapy; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D050476:Bowman Capsule / Q000166:cytology*; D051927:CD24 Antigen / Q000096:biosynthesis; D002469:Cell Separation / Q000379:methods*; D002999:Clone Cells; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D039902:Multipotent Stem Cells / Q000166:cytology*; D009687:Nuclear Proteins / Q000096:biosynthesis; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D010455:Peptides; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis
D000071916:AC133 Antigen; D015703:Antigens, CD; C069077:BMI1 protein, human; D051927:CD24 Antigen; D006023:Glycoproteins; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1