Essential but differential role for CXCR4 and CXCR7 in the therapeutic homing of human renal progenitor cells

Benedetta Mazzinghi, Elisa Ronconi, Elena Lazzeri, Costanza Sagrinati, Lara Ballerini, Maria Lucia Angelotti, Eliana Parente, Rosa Mancina, Giuseppe Stefano Netti, Francesca Becherucci, Mauro Gacci, Marco Carini, Loreto Gesualdo, Mario Rotondi, Enrico Maggi, Laura Lasagni, Mario Serio, Sergio Romagnani, Paola Romagnani

Research output: Contribution to journalArticlepeer-review

Abstract

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. JEM

Original languageEnglish
Pages (from-to)479-490
Number of pages12
JournalJournal of Experimental Medicine
Volume205
Issue number2
DOIs
Publication statusPublished - Feb 18 2008

ASJC Scopus subject areas

  • Immunology

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