Mobilization of Pluripotent Multilineage-Differentiating Stress-Enduring Cells in Ischemic Stroke

Abstract

This prospective study was aimed to prove the hypothesis that multilineage-differentiating stress-enduring (Muse) cells are mobilized from bone marrow into peripheral blood in patients with ischemic stroke. This study included 29 patients with ischemic stroke. To quantify the circulating Muse cells, peripheral blood was obtained from all patients on admission and at days 7 and 30. Using fluorescence-activated cell sorting, Muse cells were identified as stage-specific embryonic antigen-3-positive cells. The control values were obtained from 5 healthy volunteers. Separately, immunohistochemistry was performed to evaluate the distribution of Muse cells in the bone marrow of 8 autopsy cases. The number of Muse cells robustly increased within 24 hours after the onset, compared with the controls, but their baseline number and temporal profile widely varied among patients. No clinical data predicted the baseline number of Muse cells at the onset. Multivariate analysis revealed that smoking and alcohol intake significantly affect the increase in circulating Muse cells. The odds ratio was .0027 (P = .0336) and 1688 (P = .0220) for smoking and alcohol intake, respectively. The percentage of Muse cells in the bone marrow was .20% ± .17%. This study shows that pluripotent Muse cells are mobilized from the bone marrow into peripheral blood in the acute stage of ischemic stroke. Smoking and alcohol intake significantly affect their temporal profile. Therapeutic interventions that increase endogenous Muse cells or exogenous administration of Muse cells may improve functional outcome after ischemic stroke.