Abstract 1276: Pluripotent Bone Marrow (BM)-Derived Very Small Embryonic-Like (VSEL) Stem Cells are Mobilized after Acute Myocardial Infarction in Mice
Recently, we have identified in bone marrow (BM) a population of SSEA-1+/Oct-4+/Sca-1+/lin-/CD45- pluripotent, very small embryonic-like stem cells (VSELs) with the ability to differentiate into cardiac lineage in vitro. The pathophysiologic role of these cells in acute myocardial infarction (AMI) is unknown. The aim of this study was to investigate if VSELs are mobilized into peripheral blood (PB) after AMI. C57BL/6 mice (6- or 15-wk-old) underwent a 30-min coronary occlusion followed by reperfusion and were euthanized at 24 h, 48 h, or 7 days after AMI. PB samples were collected for flow cytometric, confocal microscopic, and RQ-PCR analysis. Sham controls underwent sham surgery (1-h open-chest state) while controls did not. By flow cytometry, VSELs were barely detectable in PB under baseline conditions but increased significantly after AMI, peaking at 48 h post AMI both in young (6-wk-old) and older (15-wk-old) mice (3.33±0.37 and 7.73±1.02 cells/μl of PB, respectively) (Fig 1A⇓). In contrast to hematopoietic stem cells (HSCs), sorted PB-derived VSELs were positive for Oct-4 and negative for CD45 (Fig 1B⇓). Furthermore, RQ-PCR analysis revealed increased level of mRNA for markers of pluripotency, such as Oct-4, Nanog, Rex-1, Dppa1, and Rif1, in total PB cells of 6-wk-old mice at 48 h after AMI (9.50, 6.04, 5.28, 3.18 and 2.07-fold increase as compared with sham control, respectively). This is the first report that pluripotent stem cells (VSELs) are mobilized from the bone marrow into the peripheral blood after AMI in both young and older animals. Mobilization of VSELs with cardiogenic potential raises the possibility that these cells may play a role in repair of infarcted myocardium.