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Cell Stem Cell. 2009 Apr 3;4(4):313-23. doi: 10.1016/j.stem.2009.02.013.

Synergy between CD26/DPP-IV inhibition and G-CSF improves cardiac function after acute myocardial infarction.

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1
Medical Department I, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.

Abstract

Ischemic cardiomyopathy is one of the main causes of death, which may be prevented by stem cell-based therapies. SDF-1alpha is the major chemokine attracting stem cells to the heart. Since SDF-1alpha is cleaved and inactivated by CD26/dipeptidylpeptidase IV (DPP-IV), we established a therapeutic concept--applicable to ischemic disorders in general--by combining genetic and pharmacologic inhibition of DPP-IV with G-CSF-mediated stem cell mobilization after myocardial infarction in mice. This approach leads to (1) decreased myocardial DPP-IV activity, (2) increased myocardial homing of circulating CXCR-4+ stem cells, (3) reduced cardiac remodeling, and (4) improved heart function and survival. Indeed, CD26 depletion promoted posttranslational stabilization of active SDF-1alpha in heart lysates and preserved the cardiac SDF-1-CXCR4 homing axis. Therefore, we propose pharmacological DPP-IV inhibition and G-CSF-based stem cell mobilization as a therapeutic concept for future stem cell trials after myocardial infarction.

PMID:
19341621
DOI:
10.1016/j.stem.2009.02.013
[Indexed for MEDLINE]
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