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.
Key Words
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References
- Preventing stroke: saving lives around the world.Lancet Neurol. 2007; 6: 182-187
- The great migration of bone marrow-derived stem cells toward the ischemic brain: therapeutic implications for stroke and other neurological disorders.Prog Neurobiol. 2011; 95: 213-228
- Bone marrow stromal cell transplantation for ischemic stroke—its multi-functional feature.Acta Neurobiol Exp (Wars). 2013; 73: 57-65
- Unique multipotent cells in adult human mesenchymal cell populations.Proc Natl Acad Sci USA. 2010; 107: 8639-8643
- Multilineage-differentiating stress-enduring (Muse) cells are a primary source of induced pluripotent stem cells in human fibroblasts.Proc Natl Acad Sci USA. 2011; 108: 9875-9880
- Therapeutic effects of human multilineage-differentiating stress enduring (MUSE) cell transplantation into infarct brain of mice.PLoS ONE. 2015; 10: e0116009
- Human adipose tissue possesses a unique population of pluripotent stem cells with nontumorigenic and low telomerase activities: potential implications in regenerative medicine.Stem Cells Dev. 2014; 23: 717-728
- Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy.Ann Hematol. 2010; 89: 701-713
- Cells expressing early cardiac markers reside in the bone marrow and are mobilized into the peripheral blood after myocardial infarction.Circ Res. 2004; 95: 1191-1199
- Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction.Circulation. 2004; 110: 3213-3220
- Clinical evidence that very small embryonic-like stem cells are mobilized into peripheral blood in patients after stroke.Stroke. 2009; 40: 1237-1244
- Cardiovascular event rates in patients with ST-elevation myocardial infarction were lower with early increases in mobilization of Oct4(high)Nanog(high) stem cells into the peripheral circulation during a 4-year follow-up.Int J Cardiol. 2013; 168: 2533-2539
- Circulating CD34-positive cells provide an index of cerebrovascular function.Circulation. 2004; 109: 2972-2975
- CD34/CXCR4 stem cell dynamics in acute stroke patients.Folia Neuropathol. 2012; 50: 140-146
- Neurological and functional recovery in human stroke are associated with peripheral blood CD34+ cell mobilization.J Neurol. 2007; 254: 327-332
- Increase of circulating endothelial progenitor cells in patients with coronary artery disease after exercise-induced ischemia.Arterioscler Thromb Vasc Biol. 2004; 24: 684-690
- Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease.Circ Res. 2001; 89: E1-E7
- Higher numbers of circulating endothelial progenitor cells in stroke patients with intracranial arterial stenosis.BMC Neurol. 2013; 13: 161
- Smoking decreases the level of circulating CD34+ progenitor cells in young healthy women—a pilot study.BMC Womens Health. 2010; 10: 20
- Difference in mobilization of progenitor cells after myocardial infarction in smoking versus non-smoking patients: insights from the BONAMI trial.Stem Cell Res Ther. 2013; 4: 152
- Stem cell niches exposed to tobacco smoke.Przegl Lek. 2012; 69: 1063-1073
- Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells.Nat Med. 2003; 9: 1370-1376
- Moderate levels of ethanol induce expression of vascular endothelial growth factor and stimulate angiogenesis.Am J Physiol Regul Integr Comp Physiol. 2001; 281: R365-R372
- The non-alcoholic fraction of beer increases stromal cell derived factor 1 and the number of circulating endothelial progenitor cells in high cardiovascular risk subjects: a randomized clinical trial.Atherosclerosis. 2014; 233: 518-524
- Moderate intake of red wine improves ischemia-induced neovascularization in diabetic mice—roles of endothelial progenitor cells and nitric oxide.Atherosclerosis. 2010; 212: 426-435
Article info
Publication history
Published online: March 24, 2016
Accepted:
December 27,
2015
Received in revised form:
December 11,
2015
Received:
September 22,
2015
Footnotes
Grant support: This study was supported by a grant-in-aid from the Ministry of Education, Science and Culture of Japan (No. 25293305).
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.12.033
Copyright
© 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
