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Isolation and Flow Cytometric Analysis of Immune Cells from the Ischemic Mouse Brain
Published on: February 12, 2016
Mobilization of Pluripotent Multilineage-Differentiating Stress-Enduring Cells in Ischemic Stroke
Emiko Hori1, Yumiko Hayakawa2, Tomohide Hayashi2
1Department of Neurosurgery, Graduate School of Medicine and Pharmacological Sciences, University of Toyama, Toyama, Japan; Department of Neurosurgery, Saiseikai Toyama Hospital, Toyama, Japan.
Goal:
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.
Materials And Methods:
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.
Findings:
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%.
Conclusion:
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.
Insights
Multilineage-differentiating stress-enduring (Muse) cells mobilize from bone marrow to blood after ischemic stroke. Smoking and alcohol intake influence Muse cell levels, suggesting potential therapeutic targets for stroke recovery.
Area of Science:
- Stem Cell Biology
- Neurology
- Regenerative Medicine
Background:
- Multilineage-differentiating stress-enduring (Muse) cells are pluripotent stem cells with regenerative potential.
- Mobilization of endogenous stem cells is a key factor in tissue repair following injury.
Purpose of the Study:
- To investigate the mobilization of Muse cells from bone marrow into peripheral blood in patients with ischemic stroke.
- To determine the factors influencing the temporal profile of circulating Muse cells.
Main Methods:
- Prospective study of 29 ischemic stroke patients, with peripheral blood sampling at admission, day 7, and day 30.
- Quantification of Muse cells using fluorescence-activated cell sorting (stage-specific embryonic antigen-3 positivity).
- Immunohistochemistry to assess Muse cell distribution in bone marrow from autopsy cases.
Main Results:
- Muse cell numbers significantly increased in peripheral blood within 24 hours post-stroke onset compared to controls.
- Baseline Muse cell levels and temporal profiles varied significantly among patients.
- Smoking and alcohol intake were identified as significant factors affecting the increase in circulating Muse cells (OR=0.0027 for smoking, OR=1688 for alcohol).
- Muse cells constituted approximately 0.20% ± 0.17% of bone marrow cells.
Conclusions:
- Pluripotent Muse cells are mobilized from bone marrow into peripheral blood during the acute phase of ischemic stroke.
- Smoking and alcohol consumption significantly impact the dynamics of Muse cell mobilization.
- Therapeutic strategies involving endogenous Muse cell enhancement or exogenous Muse cell administration hold promise for improving functional outcomes in ischemic stroke patients.
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