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Published on: July 10, 2019
Role of the SDF-1-CXCR4 axis in stem cell-based therapies for ischemic cardiomyopathy
Marc-Michael Zaruba1, Wolfgang-Michael Franz
1Riley Heart Research Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Insights
The Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 axis is crucial for stem cell homing to ischemic tissues. Inhibiting SDF-1 degradation enhances stem cell therapy effectiveness for ischemic cardiomyopathy.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Regenerative Medicine
Background:
- Ischemic disorders represent a major global health burden, with current treatments offering limited efficacy.
- The Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 (CXCR4) axis shows promise in mitigating ischemic conditions.
Purpose of the Study:
- To review the role of the SDF-1-CXCR4 axis in stem cell mobilization and migration.
- To explore the therapeutic potential of the SDF-1-CXCR4 axis in stem-cell-based treatments for ischemic cardiomyopathy.
Main Methods:
- Discussion of SDF-1-CXCR4 interactions during embryonic development and adult stem cell dynamics.
- Focus on strategies augmenting SDF-1 to enhance stem cell targeting to ischemic sites.
- Utilizing dipeptidylpeptidase IV (DPPIV) inhibition to prevent SDF-1 degradation and G-CSF for stem cell mobilization.
Main Results:
- The SDF-1-CXCR4 axis is vital for directed cell migration during development and stem cell retention/mobilization in adults.
- Upregulation of SDF-1 during hypoxia facilitates stem cell homing to damaged tissues.
- DPPIV inhibition combined with G-CSF successfully targeted CD34(+)CXCR4(+) cells to the ischemic heart, attenuating ischemic cardiomyopathy.
Conclusions:
- The SDF-1-CXCR4 axis is integral to stem cell homing in both embryonic and adult stages, particularly post-ischemia.
- Preserving SDF-1 functionality via DPPIV inhibition presents a promising strategy to improve stem cell therapies for ischemic conditions.
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.
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