Role of the SDF-1-CXCR4 axis in stem cell-based therapies for ischemic cardiomyopathy.
BACKGROUND
Ischemic disorders are the leading cause of mortality worldwide, current therapies only delay progression of the disease. Data suggest a role of the SDF-1-CXCR4 axis in attenuation of ischemic disorders.


METHODS
We discuss the importance of SDF-1-CXCR4 interactions during development and postnatal mobilization and migration of stem cells. We focus on the role of the SDF-1-CXCR4 axis in stem-cell-based applications for attenuation of ischemic cardiomyopathy.


RESULTS
During development the SDF-1-CXCR4 axis plays a critical role in gradient-guided cell movements. In adults, the SDF-1-CXCR4 axis is involved in retention and mobilization of stem cells. Since SDF-1 is upregulated during hypoxic tissue damage, strategies to augment or stabilize SDF-1 have been utilized to target blood-derived stem cells to ischemic tissue. We exploited this concept by preventing SDF-1 degradation with dipeptidylpeptidaseIV (DPPIV) inhibition and mobilization of stem cells by G-CSF after acute myocardial infarction. This targeted CD34(+)CXCR4(+) cells to ischemic heart and attenuated ischemic cardiomyopathy.


CONCLUSIONS
The SDF-1-CXCR4 axis plays a role in stem cell homing during embryogenesis and adulthood especially after ischemia. Preserving functional SDF-1 by DPPIV inhibition after ischemia may enhance stem cell therapies.
Riley Heart Research Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Marc-Michael
MM
Zaruba
Wolfgang-Michael
WM
Franz
D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D047108:Embryonic Development; D006321:Heart / Q000196:embryology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism / Q000628:therapy*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D015854:Up-Regulation
C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019718:Receptors, CXCR4; D018819:Dipeptidyl Peptidase 4