PMID- 20800644 OWN - NLM STAT- MEDLINE DCOM- 20110111 LR - 20211020 IS - 1873-2399 (Electronic) IS - 0301-472X (Print) IS - 0301-472X (Linking) VI - 38 IP - 12 DP - 2010 Dec TI - Evidence of mobilization of pluripotent stem cells into peripheral blood of patients with myocardial ischemia. PG - 1131-1142.e1 LID - 10.1016/j.exphem.2010.08.003 [doi] AB - 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. CI - Published by Elsevier Inc. FAU - Abdel-Latif, Ahmed AU - Abdel-Latif A AD - Gill Heart Institute and Division of Cardiovascular Medicine, University of Kentucky, 740 S. Limestone Street, Lexington, KY 40536-0200, USA. abdel-latif@uky.edu FAU - Zuba-Surma, Ewa K AU - Zuba-Surma EK FAU - Ziada, Khaled M AU - Ziada KM FAU - Kucia, Magdalena AU - Kucia M FAU - Cohen, Donald A AU - Cohen DA FAU - Kaplan, Alan M AU - Kaplan AM FAU - Van Zant, Gary AU - Van Zant G FAU - Selim, Samy AU - Selim S FAU - Smyth, Susan S AU - Smyth SS FAU - Ratajczak, Mariusz Z AU - Ratajczak MZ LA - eng GR - R01 DK074720-04/DK/NIDDK NIH HHS/United States GR - R01 DK074720/DK/NIDDK NIH HHS/United States GR - R01 HL078663/HL/NHLBI NIH HHS/United States GR - NIH R01 DK074720/DK/NIDDK NIH HHS/United States GR - R01 CA106281/CA/NCI NIH HHS/United States GR - R01 CA106281-05/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100826 PL - Netherlands TA - Exp Hematol JT - Experimental hematology JID - 0402313 RN - 0 (Cytokines) RN - 0 (Octamer Transcription Factor-3) RN - 0 (POU5F1 protein, human) RN - 0 (Stage-Specific Embryonic Antigens) RN - 0 (stage-specific embryonic antigen-4) SB - IM MH - Adult MH - Age Factors MH - Aged MH - Cytokines/blood MH - Female MH - Flow Cytometry MH - *Hematopoietic Stem Cell Mobilization MH - Humans MH - Immunophenotyping MH - Male MH - Middle Aged MH - Myocardial Ischemia/*blood/therapy MH - Octamer Transcription Factor-3/analysis MH - Pluripotent Stem Cells/*physiology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stage-Specific Embryonic Antigens/analysis PMC - PMC2992878 MID - NIHMS246525 EDAT- 2010/08/31 06:00 MHDA- 2011/01/12 06:00 PMCR- 2011/12/01 CRDT- 2010/08/31 06:00 PHST- 2010/03/22 00:00 [received] PHST- 2010/07/08 00:00 [revised] PHST- 2010/08/11 00:00 [accepted] PHST- 2010/08/31 06:00 [entrez] PHST- 2010/08/31 06:00 [pubmed] PHST- 2011/01/12 06:00 [medline] PHST- 2011/12/01 00:00 [pmc-release] AID - S0301-472X(10)00367-X [pii] AID - 10.1016/j.exphem.2010.08.003 [doi] PST - ppublish SO - Exp Hematol. 2010 Dec;38(12):1131-1142.e1. doi: 10.1016/j.exphem.2010.08.003. Epub 2010 Aug 26.