SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells

Elena De Falco, Daniele Porcelli, Anna Rita Torella, Stefania Straino, Maria Grazia Iachininoto, Alessia Orlandi, Silvia Truffa, Paolo Biglioli, Monica Napolitano, Maurizio C. Capogrossi, Maurizio Pesce

Research output: Contribution to journalArticle

Abstract

Chemokine stromal derived factor 1 (SDF-1) is involved in trafficking of hematopoietic stem cells (HSCs) from the bone marrow (BM) to peripheral blood (PB) and has been found to enhance postischemia angiogenesis. This study was aimed at investigating whether SDF-1 plays a role in differentiation of BM-derived c-kit+ stem cells into endothelial progenitor cells (EPCs) and in ischemia-induced trafficking of stem cells from PB to ischemic tissues. We found that SDF-1 enhanced EPC number by promoting α2, α4, and α5 integrin-mediated adhesion to fibronectin and collagen I. EPC differentiation was reduced in mitogen-stimulated c-kit+ cells, while cytokine withdrawal or the overexpression of the cyclin-dependent kinase (CDK) inhibitor p16INK4 restored such differentiation, suggesting a link between control of cell cycle and EPC differentiation. We also analyzed the time course of SDF-1 expression in a mouse model of hind-limb ischemia. Shortly after femoral artery dissection, plasma SDF-1 levels were up-regulated, while SDF-1 expression in the bone marrow was down-regulated in a timely fashion with the increase in the percentage age of PB progenitor cells. An increase in ischemic tissue expression of SDF-1 at RMA and protein level was also observed. Finally, using an in vivo assay such as injection of matrigel plugs, we found that SDF-1 improves formation of tubulelike structures by coinjected c-kit+ cells. Our findings unravel a function for SDF-1 in increase of EPC number and formation of vascular structures by bone marrow progenitor cells.

Original languageEnglish
Pages (from-to)3472-3482
Number of pages11
JournalBlood
Volume104
Issue number12
DOIs
Publication statusPublished - Dec 1 2004

ASJC Scopus subject areas

  • Hematology

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    De Falco, E., Porcelli, D., Torella, A. R., Straino, S., Iachininoto, M. G., Orlandi, A., Truffa, S., Biglioli, P., Napolitano, M., Capogrossi, M. C., & Pesce, M. (2004). SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells. Blood, 104(12), 3472-3482. https://doi.org/10.1182/blood-2003-12-4423