
Characterization of Renal Progenitors Committed Toward Tubular Lineage and Their Regenerative Potential in Renal Tubular Injury
Author(s) -
Angelotti Maria Lucia,
Ronconi Elisa,
Ballerini Lara,
Peired Anna,
Mazzinghi Benedetta,
Sagrinati Costanza,
Parente Eliana,
Gacci Mauro,
Carini Marco,
Rotondi Mario,
Fogo Agnes B.,
Lazzeri Elena,
Lasagni Laura,
Romagnani Paola
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1130
Subject(s) - cd24 , progenitor cell , microbiology and biotechnology , population , kidney , biology , progenitor , renal stem cell , proximal tubule , pathology , epithelium , stem cell , medicine , endocrinology , cancer stem cell , environmental health
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. S TEM C ELLS 2012;30:1714–1725