Abstract

Bone marrow‐derived progenitor cells are mobilized into the peripheral blood after acute myocardial injury and in chronic ischemic heart disease. However, the mechanisms responsible for this mobilization are poorly understood. We examined the relationship between plasma levels of bioactive lipids and number of circulating progenitor cells (CPCs) in patients (N = 437) undergoing elective or emergent cardiac catheterization. Plasma levels of sphingosine‐1 phosphate (S1P) and ceramide‐1 phosphate (C1P) were quantified using mass spectrometry. CPCs were assessed using flow cytometry. S1P levels correlated with the numbers of CD34+, CD34+/CD133+, and CD34+/CXCR4+ CPCs even after adjustment for potential confounding factors. However, no significant correlation was observed between C1P levels and CPC count. Plasma levels of S1P correlated with the number of CPCs in patients with coronary artery disease, suggesting an important mechanistic role for S1P in stem cell mobilization. The therapeutic effects of adjunctive S1P therapy to mobilize endogenous stem cells need to be investigated. Stem Cells Translational Medicine 2017;6:731–735

Highlights

  • Circulating progenitor cells (CPCs) are mononuclear cells that originate primarily from the bone marrow, differentiate into hematopoietic and endothelial cells, and contribute to vascular repair and cardiomyocyte regeneration [1,2,3,4,5]

  • The role of bone marrow-derived progenitor cells in cardiac repair is still being studied in randomized trials; strong evidence suggests that CPCs are mobilized after cardiac injury [17, 18]

  • In the largest cohort to date examining the relationship between plasma bioactive lipids and circulating stem cells, we demonstrated a strong correlation between plasma sphingosine-1 phosphate (S1P) levels and the number of CPCs in patients with coronary artery disease (CAD)

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Summary

Introduction

Circulating progenitor cells (CPCs) are mononuclear cells that originate primarily from the bone marrow, differentiate into hematopoietic and endothelial cells, and contribute to vascular repair and cardiomyocyte regeneration [1,2,3,4,5]. Studies using CPC mobilization as a method to enhance cardiac recovery in heart failure or after myocardial infarction have achieved modest success, probably because of incomplete understanding of the mechanisms underlying mobilization and homing of regenerative cells. Several chemokines, including vascular endothelial growth factor (VEGF) and stromal cell derived factor-1 (SDF-1), play an important role in the recruitment of CPCs from the bone marrow [8, 9]. After acute myocardial infarction (AMI), matrix metalloproteinases (MMPs) and proteases are upregulated in the myocardium [11], leading to the degradation of several chemokines [12]. Bioactive lipids, notably sphingosine-1 phosphate (S1P), that are resistant to MMPs have been characterized as chemoattractants that enhance mobilization and homing of stem cells from the bone marrow [13, 14]. Raising plasma S1P levels in a mouse model of AMI

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