Myeloid lineage of high proliferative potential human smooth muscle outgrowth cells circulating in blood and vasculogenic smooth muscle-like cells in vivo

Emerging experimental data supports a circulating precursor origin for some smooth muscle cells that participate in vasculogenesis but uncertainty exists on the precise phenotype and lineage of these vascular precursors. We determined the lineage of human smooth muscle outgrowth cells (SOC) derived from circulating blood mononuclear cells and smooth muscle-like cells present in regions of vasculogenesis in diseased arteries. Immunophenotypic characterization of SOC was performed using FACS and immunofluorescence (IF). An SOC hierarchy was determined based on in vitro clonogenic and proliferative potential. Lineage of smooth muscle-like cells in vasculogenic regions in vivo was also determined by dual IF for myeloid and smooth muscle specific markers combined with FISH for the X and Y chromosome in diseased vessel of human subjects who had undergone gender mismatched cardiac transplantation. We show here that primary high proliferative potential smooth muscle outgrowth cells (HPP-SOC) expanded in culture from human peripheral blood mononuclear cells (PBMC) and recipient-derived chimeric smooth muscle cells participating in vasculogenesis in vivo share a myeloid phenotype (CD68 and CD14 positivity). Moreover, HPP-SOC in vitro are distinct in being negative for several myeloid markers such as CD11b, CD13 and CD33, and CD45 surface antigens and chimeric SMC in vivo show no evidence of cell fusion propensity. This study provides evidence of a possible myeloid subpopulation origin for smooth muscle outgrowth cells in blood and vasculogenic smooth muscle-like cells in the intima and adventitial microvasculature of diseased arteries. These data have significant implications for understanding the role myeloid cells play in smooth muscle cell biology and vascular remodelling.