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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Chemokine CXCL12 / metabolism*
  • Dipeptidyl Peptidase 4 / genetics
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors*
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Heart / drug effects*
  • Heart / physiology
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / physiology*
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / enzymology
  • Myocardial Infarction / physiopathology
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology
  • Receptors, CXCR4 / metabolism*


  • Chemokine CXCL12
  • Dipeptidyl-Peptidase IV Inhibitors
  • Receptors, CXCR4
  • Granulocyte Colony-Stimulating Factor
  • Dipeptidyl Peptidase 4