Increase in circulating bone marrow progenitor cells after myocardial infarction
Daniel M Spevack1, Salvatore Cavaleri, Alexander Zolotarev
1New York University School of Medicine, New York, New York, USA. dspevack@montefiore.org
Insights
Following myocardial infarction, circulating CD34+ cells increase, indicating bone marrow progenitor cell mobilization. This suggests the heart initiates the release of these crucial repair cells in humans.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Regenerative Medicine
Background:
- Bone marrow progenitor cells expressing CD34 are crucial for repairing heart tissue after myocardial infarction.
- Mobilization of these progenitor cells into peripheral blood may aid cardiac repair.
- Investigating CD34+ cell levels post-myocardial infarction can confirm myocardial-initiated mobilization.
Purpose of the Study:
- To investigate the concentration of circulating CD34+ cells after ST-elevation myocardial infarction.
- To explore the role of specific cytokines in bone marrow progenitor cell mobilization following myocardial infarction.
Main Methods:
- Serial measurements of CD34+ cells and cytokines (HGF, SDF-1, IL-17, MCP-1, TPO) in 42 myocardial infarction patients and 15 controls.
- Blood samples collected on days 1, 4, 8, and 12 post-myocardial infarction.
- Echocardiography used to estimate infarction size.
Main Results:
- CD34+ cell concentrations significantly increased by day 8 and were sustained through day 12 post-myocardial infarction.
- Hepatocyte growth factor (HGF) showed a significant early rise, followed by a decline.
- No significant changes were observed in SDF-1, IL-17, MCP-1, or TPO levels; CD34+ cell and HGF elevations were independent of infarction size.
Conclusions:
- Elevated circulating CD34+ cells post-myocardial infarction suggest human myocardial-initiated bone marrow progenitor cell mobilization.
- The studied cytokines do not appear to directly mediate bone marrow progenitor cell mobilization in this context.
Background:
Most circulating blood cells expressing the marker CD34 are bone marrow progenitor cells. These cells differentiate into cardiomyocytes, endothelial and smooth muscle cells after myocardial infarction in vivo. Mobilization of bone marrow progenitor cells into the peripheral blood after myocardial infarction may supply these cells to the heart. Rise in CD34+ cell concentrations following myocardial infarction would support the existence of myocardial-initiated mobilization.
Methods:
Serial measurements of circulating CD34+ cells were made in 42 consecutive patients presenting with first ST-elevation myocardial infarction. Measurement of serum concentrations of monocyte chemoattractant protein-1, stromal derived factor-1, hepatocyte growth factor, interleukin-17 and thrombopoietin was also performed. Samples were drawn on day 1 after myocardial infarction, and on days 4, 8 and 12. Levels of CD34+ cells and cytokines were also measured in 15 controls.
Results:
By day 8, the mean concentration of CD34+ cells rose by 74% above mean control level of 2527 cells/ml, and 41% above day 1 mean (P=0.02). This rise was sustained on day 12 (P=0.05). On day 1, there was a 9.3-fold rise in hepatocyte growth factor above the control level of 589 pg/ml (P=0.002). Hepatocyte growth factor levels declined from the day 1 mean of 6061 to 1485 pg/ml on day 12 (P=0.002). No significant change in stromal derived factor-1, interleukin-17, monocyte chemoattractant protein-1 and thrombopoietin was observed. Elevations in CD34+ cells and hepatocyte growth factor were not related to infarction size as estimated on echocardiography.
Conclusions:
Elevation in the concentration of circulating CD34+ cells after myocardial infarction suggests that myocardial initiated bone marrow progenitor cell mobilization exists in humans. The cytokines studied in our protocol are not likely to play a direct role in bone marrow progenitor cell mobilization.
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