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Regenerative Potential of Embryonic Renal Multipotent Progenitors in Acute Renal Failure

Elena Lazzeri^*, Clara Crescioli^*, Elisa Ronconi^*, Benedetta Mazzinghi^*, Costanza Sagrinati^*, Giuseppe Stefano Netti, Maria Lucia Angelotti^*, Eliana Parente^*, Lara Ballerini^*, Lorenzo Cosmi^*, Laura Maggi^*, Loreto Gesualdo, Mario Rotondi^*,, Francesco Annunziato^*, Enrico Maggi^*, Laura Lasagni^*, Mario Serio^*, Sergio Romagnani^*, Gabriella Barbara Vannelli and Paola Romagnani^*

^* Excellence Center for Research, Transfer and High Education for the Development of DE NOVO THERAPIES, and Department of Anatomy, University of Florence, Florence, Department of Biomedical Sciences, University of Foggia, Foggia, and Department of Endocrinology and Internal Medicine, Fondazione S. Maugeri Istituti di Ricovero e Cura a Carattere Scientifico, Pavia, Italy

Correspondence: Dr. Paola Romagnani, Department of Clinical Pathophysiology, Nephrology Section, University of Florence, Viale Pieraccini 6, 50139, Firenze, Italy. Phone: 0039-055-4271356; Fax: 0039-055-4271357; E-mail: p.romagnani{at}dfc.unifi.it

Received for publication February 19, 2007. Accepted for publication July 12, 2007.

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.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673