期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 44, 期 5, 页码 865-873出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2008.02.279
关键词
very small embryonic-like stem cells; myocardial infarction; bone marrow; pluripotent; Oct-4; mobilization
资金
- NCI NIH HHS [R01 CA106281, CA-106281] Funding Source: Medline
- NHLBI NIH HHS [R01 HL072410, P01 HL078825-04, P01 HL078825-02, P01 HL078825-010001, R37 HL055757-06, HL-55757, P01 HL078825-030001, R01 HL-72410, R37 HL055757-14, P01 HL078825, P01 HL078825-03, R01 HL068088, R37 HL055757-07, R37 HL055757-08, R01 HL055757, HL-68088, R37 HL055757, R37 HL055757-10, P01 HL078825-05, R01 HL043151-10, R01 HL076794, HL-78825, R01 HL068088-03, R01 HL076794-03, R37 HL055757-09, R01 HL076794-01, P01 HL078825-020001, P01 HL078825-040001, P01 HL078825-050001, R37 HL055757-12, HL-70897, R01 HL070897-01A1, R01 HL076794-04, R37 HL055757-11, HL-76794, R01 HL055757-05, P01 HL078825-01, R01 HL076794-02, R01 HL070897, R37 HL055757-13] Funding Source: Medline
- NIDDK NIH HHS [DK-074720, R01 DK074720] Funding Source: Medline
The adult bone marrow (BM) harbors Sca-1+/Lin-/CD45-pluripotent very small embryonic-like stem cells (VSELs), which can differentiate in vitro into several lineages, including cardiac and vascular lineages. Since mobilization of stem/progenitors from the BM is a prerequisite for their participation in organ repair, we investigated whether VSELs are mobilized into the peripheral blood (PB) after acute myocardial infarction (MI). Wild-type mice (C57BL/6 strain, 6- or 15-wk-old) underwent a 30-min coronary occlusion followed by reperfusion (groups III-V, VIII-X, n=6-12/group) or a 1-hour open-chest state (sham controls, groups II and VII, n=8-12/group); mice were sacrificed 24 h, 48 h, or 7 days later and PB samples were harvested. Controls (groups I and VI, n = 6/group) were sacrificed without any intervention. By flow cytometry, VSELs were barely detectable in PB under baseline conditions but their levels increased significantly at 48 It after MI, both in younger (6-wk-old) and older (15-wk-old) mice (3.33 +/- 0.37 and 7.10 +/- 0.89 cells/mu l of blood, respectively). At 48 h after MI, qRT-PCR analysis revealed significantly increased levels of mRNA of markers of pluripotency (Oct-4, Nanog, Rex-1, Rif1, and Dppa1) in PB cells of 6-wk-old (but not 15-wk-old) infarcted mice compared with either controls or sham controls. Confocal microscopy and ImageStream analysis confirmed that mobilized VSELs expressed Oct-4 protein, while Sca-1+/Lin-/CD45+ hematopoietic stem cells did not. This is the first demonstration that Oct-4+ pluripotent stem cells (VSELs) are mobilized from the BM into the PB after acute MI. This phenomenon may have pathophysiological and therapeutic implications for repair of infarcted myocardium. (C) 2008 Elsevier Inc. All rights reserved.
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