Objective: The ischemic myocardium releases multiple chemotactic factors responsible for the mobilization and recruitment of bone marrow-derived cells to injured myocardium. However, the mobilization of primitive pluripotent stem cells (PSCs) enriched in very small embryonic-like stem cells (VSELs) in various cardiac ischemic scenarios is not well understood. Materials and Methods: Fifty-four ischemic heart disease patients, including subjects with stable angina, non-ST elevation myocardial infarction, and ST elevation myocardial infarction (STEMI) and 12 matched controls were enrolled. The absolute numbers of circulating stem/primitive cells in samples of peripheral blood (PB) were quantitated by ImageStream analysis and conventional flow cytometry. Gene expression of PSC (Oct-4 and Nanog), early cardiomyocyte (Nkx-2.5 and GATA-4), and endothelial (von Willebrand factor) markers was analyzed by real-time polymerase chain reaction. Results: The absolute numbers of PSCs, stem cell populations enriched in VSELs, and hematopoietic stem cells present in PB were significantly higher in STEMI patients at presentation and declined over time. There was a corresponding increase in pluripotent, cardiac, and endothelial gene expression in unfractionated PB cells and sorted PB-derived primitive CD34+ cells. The absolute numbers of circulating VSELs and hematopoietic stem cells in STEMI correlated negatively with patient age. Conclusions: Myocardial ischemia mobilizes primitive PSCs including pluripotent VSELs into the circulation. The peak of mobilization occurs within 12 hours in patients presenting with STEMI, which may represent a therapeutic window for future clinical applications. Reduced stem cell mobilization with advancing age could explain, in part, the observation that age is associated with poor prognosis in patients with myocardial infarction.
|State||Published - Dec 2010|
Bibliographical noteFunding Information:
Drs. Abdel-Latif and Ziada are supported by the University of Kentucky Clinical and Translational Science Pilot Award . Dr. Zuba-Surma is supported by the “Polish Foundation of Science” homing program grant number 2008/15 . Dr. Ratajczak is supported by National Institutes of Health grant R01 CA106281, NIH R01 DK074720 , EU structural funds , Innovative Economy Operational Program ( POIG.01.01.02-00-109/09-00 ), and Stella and Henry Endowment.
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
- Cancer Research