Abstract 697: Mobilization of Oct-4+ Bone Marrow-Derived Very Small Embryonic-Like Stem Cells in Patients with Acute Myocardial Infarction
Bone marrow-derived CD34+ CXCR4+ progenitor cells are mobilized into peripheral blood early in acute myocardial infarction (MI). Adult murine bone marrow contains population of small CD34+ lin−CD45−CXCR4+ cells expressing markers of pluripotent stem cells (PSC) SSEA, Oct-4 and Nanog. This population of very small embryonic-like cells (VSEL) has unique morphology (small size 2– 4 μm, large nucleus, euchromatin) and capability to form embrioid bodies (EB). Murine EB-derived cells can in vitro differentiate into cells from all three germ layers including cardiomyocytes. We hypothesized that in patients with acute MI small cells expressing the VSEL immunophenotype and PSC markers are present in bone marrow and mobilized into peripheral blood. Blood samples (20 mL) from 18 patients with acute MI were obtained after 12 hours, 2 and 5 days after symptoms onset. Bone marrow samples (20 mL) were obtained from 2 patients with acute MI and 3 healthy volunteers. Mononuclear cells were isolated using hypotonic lysis and samples were analyzed by FACS. Mobilization of following cell populations was confirmed: hematopoietic lin−CD45+ CXCR4+, lin−CD45+CD133+, lin−CD45+CD34+ and non-hematopoietic (VSEL) lin−CD45−CXCR4+, lin−CD45−CD133+, lin−CD45−CD34+. Analysis of the cell number using lymphocyte gate showed more significant increase of CD45+ (hematopoietic) populations of lin−CD34+, lin−CD133+ and lin−CXCR4+ cells. After gating for small events (VSEL size range) we found more significant mobilization of small, non-hematopoietic populations of lin−CD34+, lin−CD133+ and lin−CXCR4+ cells (Table⇓). The expression of PSC markers (Oct-4, Nanog, SSEA-1) in VSEL was confirmed using real-time RT-PCR.
Conclusion: We report for the first time that acute MI is associated with mobilization of non-hematopoietic VSELs expressing pluripotent stem cells markers.