title: Characterization of renal progenitors committed toward tubular lineage and their regenerative potential in renal tubular injury.
abstract: Recent studies implicated the existence in adult human kidney of a population of renal progenitors with the potential to regenerate glomerular as well as tubular epithelial cells and characterized by coexpression of surface markers CD133 and CD24. Here, we demonstrate that CD133+CD24+ renal progenitors can be distinguished in distinct subpopulations from normal human kidneys based on the surface expression of vascular cell adhesion molecule 1, also known as CD106. CD133+CD24+CD106+ cells were localized at the urinary pole of Bowman's capsule, while a distinct population of scattered CD133+CD24+CD106- cells was localized in the proximal tubule as well as in the distal convoluted tubule. CD133+CD24+CD106+ cells exhibited a high proliferative rate and could differentiate toward the podocyte as well as the tubular lineage. By contrast, CD133+CD24+CD106- cells showed a lower proliferative capacity and displayed a committed phenotype toward the tubular lineage. Both CD133+CD24+CD106+ and CD133+CD24+CD106- cells showed higher resistance to injurious agents in comparison to all other differentiated cells of the kidney. Once injected in SCID mice affected by acute tubular injury, both of these populations displayed the capacity to engraft within the kidney, generate novel tubular cells, and improve renal function. These properties were not shared by other tubular cells of the adult kidney. Finally, CD133+CD24+CD106- cells proliferated upon tubular injury, becoming the predominating part of the regenerating epithelium in patients with acute or chronic tubular damage. These data suggest that CD133+CD24+CD106- cells represent tubular-committed progenitors that display resistance to apoptotic stimuli and exert regenerative potential for injured tubular tissue.
authors.affiliation: Excellence Centre for Research, Transfer and High Education for the development of DE NOVO Therapies, University of Florence, Florence, Italy.
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Angelotti
authors.forename: Elisa
authors.initials: E
authors.lastname: Ronconi
authors.forename: Lara
authors.initials: L
authors.lastname: Ballerini
authors.forename: Anna
authors.initials: A
authors.lastname: Peired
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mazzinghi
authors.forename: Costanza
authors.initials: C
authors.lastname: Sagrinati
authors.forename: Eliana
authors.initials: E
authors.lastname: Parente
authors.forename: Mauro
authors.initials: M
authors.lastname: Gacci
authors.forename: Marco
authors.initials: M
authors.lastname: Carini
authors.forename: Mario
authors.initials: M
authors.lastname: Rotondi
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Fogo
authors.forename: Elena
authors.initials: E
authors.lastname: Lazzeri
authors.forename: Laura
authors.initials: L
authors.lastname: Lasagni
authors.forename: Paola
authors.initials: P
authors.lastname: Romagnani
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007668:Kidney / Q000166:cytology*; D007674:Kidney Diseases / Q000378:metabolism; D007683:Kidney Tubular Necrosis, Acute / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D018613:Microscopy, Confocal; D012038:Regeneration / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014183:Transplantation, Heterologous