FUNCTIONAL RECOVERY AFTER HEMATIC ADMINISTRATION OF ALLOGENIC MESENCHYMAL STEM CELLS IN ACUTE ISCHEMIC STROKE IN RATS

被引:117
作者
Gutierrez-Fernandez, M. [2 ]
Rodriguez-Frutos, B. [2 ]
Alvarez-Grech, J. [2 ]
Vallejo-Cremades, M. T. [2 ]
Exposito-Alcaide, M. [2 ]
Merino, J. [2 ,3 ]
Roda, J. M. [4 ]
Diez-Tejedor, E. [1 ,2 ]
机构
[1] Univ Autonoma Madrid, Sch Med, Dept Neurol, Stroke Ctr,Hosp La Paz,IdiPAZ,Hlth Res Inst, Madrid 28046, Spain
[2] Univ Autonoma Madrid, Sch Med, Hosp La Paz, Neurosci & Cerebrovasc Res Lab,IdiPAZ,Hlth Res In, Madrid 28046, Spain
[3] Univ Autonoma Madrid, Sch Med, Hosp La Paz, IdiPAZ,Hlth Res Inst,Dept Expt Surg, Madrid 28046, Spain
[4] Univ Autonoma Madrid, Sch Med, Hosp La Paz, IdiPAZ,Hlth Res Inst,Dept Neurosurg, Madrid 28046, Spain
关键词
acute ischemic stroke; i.v. and intracarotid administration routes; mesenchymal stem cells; neurological evaluation; brain damage; FOCAL CEREBRAL-ISCHEMIA; MARROW STROMAL CELLS; BONE-MARROW; ARTERY OCCLUSION; PROGENITOR CELLS; BRAIN; EXPRESSION; MODEL; TRANSPLANTATION; INJURY;
D O I
10.1016/j.neuroscience.2010.11.054
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Hematic administration of bone marrow-derived mesenchymal stem cells (MSCs) in acute ischemic stroke may not only be an effective reparative treatment but also a brain protective therapy that improves neurological recovery. Our purpose was to study whether either iv. or intracarotid (i.c.) administration of allogenic MSCs during the acute phase were effective in improving neurological recovery and decreasing brain damage in an experimental rat model. In a model of permanent middle cerebral artery occlusion (pMCAO), we analyzed: neurological evaluation; MSCs migration and implantation; interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels; lesion volume; cell death; cellular proliferation; vascular endothelial growth factor (VEGF) expression and blood vessel number. Regardless of the administration route, treated groups showed better neurological recovery, without significant differences between the two groups. Migration and implantation of MSCs in the lesion area was observed in animals receiving i.c. but not i.v. treatment. The highest cytokine values were observed in the i.v. MSCs and i.c. control groups, and these levels were significantly different from the corresponding i.v. control and i.c. MSCs groups, respectively. In addition, there were significant differences between the i.v. MSCs and i.c. MSCs groups in IL-6 levels. Neither treatment reduced infarction volume. However, cell death, measured as TUNEL+ cells was decreased with significant differences between control groups. BrdU+ cells were also significantly increased in the peri-infarct zone at 14 days. VEGF expression was significantly higher in the i.c. MSCs group than in the i.c. control group and blood vessel number was significantly higher in treated groups than control groups with significant differences in the pen-infarct zone at 14 days. We conclude that allogenic MSCs administration shows therapeutic efficacy in our acute ischemic stroke model. Both routes demonstrably improved neurological recovery and provided brain protection. Crown Copyright (c) 2011 Published by Elsevier Ltd on behalf of IBRO. All rights reserved.
引用
收藏
页码:394 / 405
页数:12
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