title: Evidence of mobilization of pluripotent stem cells into peripheral blood of patients with myocardial ischemia.
abstract: 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.
authors.affiliation: Gill Heart Institute and Division of Cardiovascular Medicine, University of Kentucky, 740 S. Limestone Street, Lexington, KY 40536-0200, USA. abdel-latif@uky.edu
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdel-Latif
authors.forename: Ewa K
authors.initials: EK
authors.lastname: Zuba-Surma
authors.forename: Khaled M
authors.initials: KM
authors.lastname: Ziada
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kucia
authors.forename: Donald A
authors.initials: DA
authors.lastname: Cohen
authors.forename: Alan M
authors.initials: AM
authors.lastname: Kaplan
authors.forename: Gary
authors.initials: G
authors.lastname: Van Zant
authors.forename: Samy
authors.initials: S
authors.lastname: Selim
authors.forename: Susan S
authors.initials: SS
authors.lastname: Smyth
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
mesh_terms: 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
chemical_list: 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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