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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
- Source :
- Oncotarget
- Publication Year :
- 2016
- Publisher :
- Impact Journals, LLC, 2016.
-
Abstract
- // Kuan-Hung Chen 1,8,* , Chih-Hung Chen 2,* , Christopher Glenn Wallace 3 , Chun-Man Yuen 4 , Gour-Shenq Kao 5 , Yi-Ling Chen 5 , Pei-Lin Shao 6 , Yung-Lung Chen 5 , Han-Tan Chai 5 , Kun-Chen Lin 1 , Chu-Feng Liu 7 , Hsueh-Wen Chang 8 , Mel S. Lee 9 and Hon-Kan Yip 5,6,10,11,12 1 Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Department of Internal Medicine, Division of General Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 3 Department of Plastic Surgery, University Hospital of South Manchester, Manchester, UK 4 Department of Surgery, Division of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Internal Medicine, Division of Cardiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 6 Department of Nursing, Asia University, Taichung, Taiwan 7 Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 8 Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 9 Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 10 Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 11 Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 12 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan * These authors have contributed equally to this work Correspondence to: Hon-Kan Yip, email: // Keywords : xenogenic adipose-derived mesenchymal stem cell, exosomes, ischemic stroke, brain infarct size, neurological function, Pathology Section Received : August 15, 2016 Accepted : October 14, 2016 Published : October 25, 2016 Abstract 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 ( 100 &#x 3 bc;g)], 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.
- Subjects :
- Male
0301 basic medicine
Gerontology
medicine.medical_specialty
xenogenic adipose-derived mesenchymal stem cell
brain infarct size
Neurological function
Glial Fibrillary Acid Protein
exosomes
Mesenchymal Stem Cell Transplantation
neurological function
03 medical and health sciences
0302 clinical medicine
Left middle cerebral artery
Internal medicine
Pathology Section
ischemic stroke
medicine
Animals
Acute ischemic stroke
Biological sciences
business.industry
Brain
Mesenchymal Stem Cells
University hospital
Magnetic Resonance Imaging
Research Paper: Pathology
Rats
Stroke
Disease Models, Animal
Oxidative Stress
Treatment Outcome
030104 developmental biology
Adipose Tissue
Oncology
Brain infarction
Ischemic stroke
Heterografts
Administration, Intravenous
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....1911ade024cd79d7b98817d52bb016be