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¹ Excellence Center for Research, Transfer and High Education DENOthe, and ² Department of Medical and Surgical Critical Care, University of Florence, 50121 Florence, Italy
³ Department of Biomedical Sciences, University of Foggia, 71100 Foggia, Italy
⁴ Department of Endocrinology and Internal Medicine, Fondazione Salvatore Maugeri Istituto Di Ricovero e Cura a Carattere Scientifico, 27100 Pavia, Italy

CORRESPONDENCE Paola Romagnani:p.romagnani{at}dfc.unifi.it

Recently, we have identified a population of renal progenitor cells in human kidneys showing regenerative potential for injured renal tissue of SCID mice. We demonstrate here that among all known chemokine receptors, human renal progenitor cells exhibit high expression of both stromal-derived factor-1 (SDF-1) receptors, CXCR4 and CXCR7. In SCID mice with acute renal failure (ARF), SDF-1 was strongly up-regulated in resident cells surrounding necrotic areas. In the same mice, intravenously injected renal stem/progenitor cells engrafted into injured renal tissue decreased the severity of ARF and prevented renal fibrosis. These beneficial effects were abolished by blocking either CXCR4 or CXCR7, which dramatically reduced the number of engrafting renal progenitor cells. However, although SDF-1–induced migration of renal progenitor cells was only abolished by an anti-CXCR4 antibody, transendothelial migration required the activity of both CXCR4 and CXCR7, with CXCR7 being essential for renal progenitor cell adhesion to endothelial cells. Moreover, CXCR7 but not CXCR4 was responsible for the SDF-1–induced renal progenitor cell survival. Collectively, these findings suggest that CXCR4 and CXCR7 play an essential, but differential, role in the therapeutic homing of human renal progenitor cells in ARF, with important implications for the development of stem cell–based therapies.

Abbreviations used: ARF, acute renal failure; BMSC, BM-derived SC; BUN, blood urea nitrogen; EBM, endothelial basal medium; EC, endothelial cell; HSC, hematopoietic SC; HUVEC, human umbilical vein EC; I-TAC, interferon-induced T cell chemoattractant; LTA, Lotus tetragonolobus agglutinin; RMP, renal multipotent progenitor; RPTEC, renal proximal tubular cell; SC, stem cell; SDF, stromal-derived factor.

B. Mazzinghi and E. Ronconi contributed equally to this paper.

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