CXCR4 expression determines functional activity of bone marrow-derived mononuclear cells for therapeutic neovascularization in acute ischemia

Florian H. Seeger, Tina Rasper, Masamichi Koyanagi, Henrik Fox, Andreas M. Zeiher, Stefanie Dimmeler

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

OBJECTIVE-: Bone marrow-derived mononuclear cells (BMCs) improve the functional recovery after ischemia. However, BMCs comprise a heterogeneous mixture of cells, and it is not known which cell types are responsible for the induction of neovascularization after cell therapy. Because cell recruitment is critically dependent on the expression of the SDF-1-receptor CXCR4, we examined whether the expression of CXCR4 may identify a therapeutically active population of BMCs. METHODS AND RESULTS-: Human CXCR4+ and CXCR4- BMCs were sorted by magnetic beads. CXCR4+ BMCs showed a significantly higher invasion capacity under basal conditions and after SDF-1 stimulation. Hematopoietic or mesenchymal colony-forming capacity did not differ between CXCR4+ and CXCR4- BMCs. Injection of CXCR4 + BMCs in mice after induction of hindlimb ischemia significantly improved the recovery of perfusion compared to injection of CXCR4+ BMCs. Likewise, capillary density was significantly increased in CXCR4 + BMC-treated mice. Because part of the beneficial effects of cell therapy were attributed to the release of paracrine effectors, we analyzed BMC supernatants for secreted factors. Importantly, supernatants of CXCR4 BMCs were enriched in the proangiogenic cytokines HGF and PDGF-BB. CONCLUSION-: CXCR4 + BMCs exhibit an increased therapeutic potential for blood flow recovery after acute ischemia. Mechanistically, their higher migratory capacity and their increased release of paracrine factors may contribute to enhanced tissue repair.

Original languageEnglish
Pages (from-to)1802-1809
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume29
Issue number11
DOIs
Publication statusPublished - Nov 1 2009

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Ischemia
Bone Marrow
Therapeutics
Cell- and Tissue-Based Therapy
CXCR4 Receptors
Injections
Hindlimb
Perfusion
Cytokines

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

CXCR4 expression determines functional activity of bone marrow-derived mononuclear cells for therapeutic neovascularization in acute ischemia. / Seeger, Florian H.; Rasper, Tina; Koyanagi, Masamichi; Fox, Henrik; Zeiher, Andreas M.; Dimmeler, Stefanie.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 29, No. 11, 01.11.2009, p. 1802-1809.

Research output: Contribution to journalArticle

Seeger, Florian H. ; Rasper, Tina ; Koyanagi, Masamichi ; Fox, Henrik ; Zeiher, Andreas M. ; Dimmeler, Stefanie. / CXCR4 expression determines functional activity of bone marrow-derived mononuclear cells for therapeutic neovascularization in acute ischemia. In: Arteriosclerosis, thrombosis, and vascular biology. 2009 ; Vol. 29, No. 11. pp. 1802-1809.
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