Regeneration of Glomerular Podocytes by Human Renal... : Journal of the American Society of Nephrology (original) (raw)

BASIC RESEARCH

Ronconi, Elisa; Sagrinati, Costanza; Angelotti, Maria Lucia; Lazzeri, Elena; Mazzinghi, Benedetta; Ballerini, Lara; Parente, Eliana; Becherucci, Francesca; Gacci, Mauro; Carini, Marco; Maggi, Enrico; Serio, Mario; Vannelli, Gabriella Barbara; Lasagni, Laura; Romagnani, Sergio; Romagnani, Paola

*Excellence Center for Research, Transfer and High Education Denothe, †Department of Medical and Surgical Critical Care, and ‡Department of Anatomy, University of Florence, Florence, Italy

Correspondence: Dr. Paola Romagnani, Department of Clinical Pathophysiology, Nephrology Section, University of Florence, Viale Pieraccini 6, 50139, Firenze, Italy. Phone: ++39554271356; Fax: ++39554271357; E-mail: [email protected]

Accepted September 21, 2008

Received July 11, 2008

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.