title: Bone marrow-derived pluripotent very small embryonic-like stem cells (VSELs) are mobilized after acute myocardial infarction.
abstract: 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 h after MI, both in younger (6-wk-old) and older (15-wk-old) mice (3.33+/-0.37 and 7.10+/-0.89 cells/microl 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.
authors.affiliation: Stem Cell Institute, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Ewa K
authors.initials: EK
authors.lastname: Zuba-Surma
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kucia
authors.forename: Buddhadeb
authors.initials: B
authors.lastname: Dawn
authors.forename: Yiru
authors.initials: Y
authors.lastname: Guo
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001773:Blood Cells; D001854:Bone Marrow Cells / Q000166:cytology*; D019070:Cell Lineage; D002469:Cell Separation; D053595:Embryonic Stem Cells / Q000166:cytology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D019650:Hematopoietic Stem Cell Mobilization; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D012333:RNA, Messenger