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Updated: May 8, 2026
Isolation and Identification of Extravascular Immune Cells of the Heart
Published on: August 23, 2018
CXCR4+ and FLK-1+ identify circulating cells associated with improved cardiac function in patients following
Rahul Suresh1, Anca Chiriac, Kashish Goel
1Mayo Medical School, College of Medicine, Rochester, MN, USA.
Insights
Circulating CD45(-)/CXCR4(+)/FLK-1(+) cells are elevated in acute myocardial infarction (AMI) patients and linked to improved heart function recovery. These cells may serve as a diagnostic and prognostic tool for cardiac regeneration after AMI.
Area of Science:
- Cardiovascular Biology
- Stem Cell Research
- Regenerative Medicine
Background:
- Biomarkers CXCR4/FLK-1 identify cardiac progenitors in experimental models.
- Translational value of these cells in human ischemic heart disease remains unknown.
Purpose of the Study:
- To identify and quantify CD45(-)/CXCR4(+)/FLK-1(+) cells in human circulation.
- To investigate the association of these cells with acute myocardial infarction (AMI) and cardiac function.
Main Methods:
- Flow cytometry was used to identify CD45(-)/CXCR4(+)/FLK-1(+) cells in healthy individuals and AMI patients.
- Echocardiography, including 2D-speckle-tracking strain analysis, assessed left ventricular (LV) systolic function.
- Cell-load was measured at various time points post-AMI.
Main Results:
- CD45(-)/CXCR4(+)/FLK-1(+) cells were detected in adult circulation.
- AMI patients exhibited higher cell-load at 48-h, 3-months, and 6-months post-AMI compared to controls.
- Higher 48-h post-AMI cell-load correlated with improved longitudinal strain and reduced dyssynchrony during follow-up.
Conclusions:
- CD45(-)/CXCR4(+)/FLK-1(+) cells are present in human circulation and increase following AMI.
- These cells are associated with improved left ventricular systolic function recovery.
- CD45(-)/CXCR4(+)/FLK-1(+) cells show potential as diagnostic and prognostic markers for cardiac regenerative capacity in AMI.
Abstract:
The biomarkers CXCR4/FLK-1 select cardiac progenitors from a stem cell pool in experimental models. However, the translational value of these cells in human ischemic heart disease is unknown. Here, flow-cytometry identified CD45(-)/CXCR4(+)/FLK-1(+) cells in 30 individuals without ischemic heart disease and 33 first-time acute myocardial infarction (AMI) patients. AMI patients had higher CD45(-)/CXCR4(+)/FLK-1(+) cell-load at 48-h and 3- and 6-months post-AMI (p = 0.003,0.04,0.04, respectively) than controls. Cardiovascular risk factors and left ventricular (LV) ejection fraction were not associated with cell-load. 2D-speckle-tracking strain echocardiography assessment of LV systolic function showed improvement in longitudinal strain and dyssynchrony during follow-up associated with longitudinal increases in and higher 48-h post-AMI CD45(-)/CXCR4(+)/FLK-1(+) cell-load (r = -0.525, p = 0.025; r = -0.457, p = 0.029, respectively). In conclusion, CD45(-)/CXCR4(+)/FLK-1(+) cells are present in adult human circulation, increased in AMI and associated with improved LV systolic function. Thus, CD45(-)/CXCR4(+)/FLK-1(+) cells may provide a diagnostic tool to follow cardiac regenerative capacity and potentially serve as a prognostic marker in AMI.
