Evidence of mobilization of pluripotent stem cells into peripheral blood of patients with myocardial ischemia.
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.


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.
Abdel-Latif
Ahmed
A
Gill Heart Institute and Division of Cardiovascular Medicine, University of Kentucky, 740 S. Limestone Street, Lexington, KY 40536-0200, USA. abdel-latif@uky.edu
Zuba-Surma
Ewa K
EK
Ziada
Khaled M
KM
Kucia
Magdalena
M
Cohen
Donald A
DA
Kaplan
Alan M
AM
Van Zant
Gary
G
Selim
Samy
S
Smyth
Susan S
SS
Ratajczak
Mariusz Z
MZ
D000328:Adult; D000367:Age Factors; D000368:Aged; D016207:Cytokines / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000628:therapy; D050814:Octamer Transcription Factor-3 / Q000032:analysis; D039904:Pluripotent Stem Cells / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055746:Stage-Specific Embryonic Antigens / Q000032:analysis
D016207:Cytokines; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D055746:Stage-Specific Embryonic Antigens; C066584:stage-specific embryonic antigen-4
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