Role of the SDF-1-CXCR4 axis in stem cell-based therapies for ischemic cardiomyopathy

Abstract

Importance of the field: 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.

Areas covered in this review: 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.

What the reader will gain: 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.

Take home message: 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.