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Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke

We tested the hypothesis that combined xenogenic (from mini-pig) adipose-derived mesenchymal stem cell (ADMSC) and ADMSC-derived exosome therapy could reduce brain-infarct zone (BIZ) and enhance neurological recovery in rat after acute ischemic stroke (AIS) induced by 50-min left middle cerebral art...

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Autores principales: Chen, Kuan-Hung, Chen, Chih-Hung, Wallace, Christopher Glenn, Yuen, Chun-Man, Kao, Gour-Shenq, Chen, Yi-Ling, Shao, Pei-Lin, Chen, Yung-Lung, Chai, Han-Tan, Lin, Kun-Chen, Liu, Chu-Feng, Chang, Hsueh-Wen, Lee, Mel S., Yip, Hon-Kan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342685/
https://www.ncbi.nlm.nih.gov/pubmed/27793019
http://dx.doi.org/10.18632/oncotarget.12902
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author Chen, Kuan-Hung
Chen, Chih-Hung
Wallace, Christopher Glenn
Yuen, Chun-Man
Kao, Gour-Shenq
Chen, Yi-Ling
Shao, Pei-Lin
Chen, Yung-Lung
Chai, Han-Tan
Lin, Kun-Chen
Liu, Chu-Feng
Chang, Hsueh-Wen
Lee, Mel S.
Yip, Hon-Kan
author_facet Chen, Kuan-Hung
Chen, Chih-Hung
Wallace, Christopher Glenn
Yuen, Chun-Man
Kao, Gour-Shenq
Chen, Yi-Ling
Shao, Pei-Lin
Chen, Yung-Lung
Chai, Han-Tan
Lin, Kun-Chen
Liu, Chu-Feng
Chang, Hsueh-Wen
Lee, Mel S.
Yip, Hon-Kan
author_sort Chen, Kuan-Hung
collection PubMed
description We tested the hypothesis that combined xenogenic (from mini-pig) adipose-derived mesenchymal stem cell (ADMSC) and ADMSC-derived exosome therapy could reduce brain-infarct zone (BIZ) and enhance neurological recovery in rat after acute ischemic stroke (AIS) induced by 50-min left middle cerebral artery occlusion. Adult-male Sprague-Dawley rats (n = 60) were divided equally into group 1 (sham-control), group 2 (AIS), group 3 [AIS-ADMSC (1.2×10(6) cells)], group 4 [AIS-exosome (100μg)], and group 5 (AIS-exosome-ADMSC). All therapies were provided intravenously at 3h after AIS procedure. BIZ determined by histopathology (by day-60) and brain MRI (by day-28) were highest in group 2, lowest in group 1, higher in groups 3 and 4 than in group 5, but they showed no difference between groups 3 and 4 (all p < 0.0001). By day-28, sensorimotor functional results exhibited an opposite pattern to BIZ among the five groups (p < 0.005). Protein expressions of inflammatory (inducible nitric oxide synthase/tumor necrosis factor-α/nuclear factor-κB/interleukin-1β/matrix metalloproteinase-9/plasminogen activator inhibitor-1/RANTES), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (caspase-3/ Poly-ADP-ribose polymerase), and fibrotic (Smad3/transforming growth factor-β) biomarkers, and cellular expressions of brain-damaged (γ-H2AX+/ XRCC1-CD90+/p53BP1-CD90+), inflammatory (CD11+/CD68+/glial fibrillary acid protein+) and brain-edema (aquaporin-4+) markers showed a similar pattern of BIZ among the groups (all n < 0.0001). In conclusion, xenogenic ADMSC/ADMSC-derived exosome therapy was safe and offered the additional benefit of reducing BIZ and improving neurological function in rat AIS.
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spelling pubmed-53426852017-03-28 Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke Chen, Kuan-Hung Chen, Chih-Hung Wallace, Christopher Glenn Yuen, Chun-Man Kao, Gour-Shenq Chen, Yi-Ling Shao, Pei-Lin Chen, Yung-Lung Chai, Han-Tan Lin, Kun-Chen Liu, Chu-Feng Chang, Hsueh-Wen Lee, Mel S. Yip, Hon-Kan Oncotarget Research Paper: Pathology We tested the hypothesis that combined xenogenic (from mini-pig) adipose-derived mesenchymal stem cell (ADMSC) and ADMSC-derived exosome therapy could reduce brain-infarct zone (BIZ) and enhance neurological recovery in rat after acute ischemic stroke (AIS) induced by 50-min left middle cerebral artery occlusion. Adult-male Sprague-Dawley rats (n = 60) were divided equally into group 1 (sham-control), group 2 (AIS), group 3 [AIS-ADMSC (1.2×10(6) cells)], group 4 [AIS-exosome (100μg)], and group 5 (AIS-exosome-ADMSC). All therapies were provided intravenously at 3h after AIS procedure. BIZ determined by histopathology (by day-60) and brain MRI (by day-28) were highest in group 2, lowest in group 1, higher in groups 3 and 4 than in group 5, but they showed no difference between groups 3 and 4 (all p < 0.0001). By day-28, sensorimotor functional results exhibited an opposite pattern to BIZ among the five groups (p < 0.005). Protein expressions of inflammatory (inducible nitric oxide synthase/tumor necrosis factor-α/nuclear factor-κB/interleukin-1β/matrix metalloproteinase-9/plasminogen activator inhibitor-1/RANTES), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (caspase-3/ Poly-ADP-ribose polymerase), and fibrotic (Smad3/transforming growth factor-β) biomarkers, and cellular expressions of brain-damaged (γ-H2AX+/ XRCC1-CD90+/p53BP1-CD90+), inflammatory (CD11+/CD68+/glial fibrillary acid protein+) and brain-edema (aquaporin-4+) markers showed a similar pattern of BIZ among the groups (all n < 0.0001). In conclusion, xenogenic ADMSC/ADMSC-derived exosome therapy was safe and offered the additional benefit of reducing BIZ and improving neurological function in rat AIS. Impact Journals LLC 2016-10-25 /pmc/articles/PMC5342685/ /pubmed/27793019 http://dx.doi.org/10.18632/oncotarget.12902 Text en Copyright: © 2016 Chen et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper: Pathology
Chen, Kuan-Hung
Chen, Chih-Hung
Wallace, Christopher Glenn
Yuen, Chun-Man
Kao, Gour-Shenq
Chen, Yi-Ling
Shao, Pei-Lin
Chen, Yung-Lung
Chai, Han-Tan
Lin, Kun-Chen
Liu, Chu-Feng
Chang, Hsueh-Wen
Lee, Mel S.
Yip, Hon-Kan
Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke
title Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke
title_full Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke
title_fullStr Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke
title_full_unstemmed Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke
title_short Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke
title_sort intravenous administration of xenogenic adipose-derived mesenchymal stem cells (admsc) and admsc-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke
topic Research Paper: Pathology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342685/
https://www.ncbi.nlm.nih.gov/pubmed/27793019
http://dx.doi.org/10.18632/oncotarget.12902
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