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Stem Cell Rev Rep ; 13(5): 670-685, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28795363

RESUMO

Stroke, as the second most common cause of death, imposes a great financial burden on both the individual and society. Mesenchymal stem cells from rodents have demonstrated efficacy in experimental animal models of stroke due to enhanced neurological recovery. Since FGF1 (fibroblast growth factor 1) displays neuroprotective properties, for the first time, we investigated the effect of acute intravenous administration of FGF1 gene transfected adipose-derived mesenchymal stem cell (AD-MSCFGF1) on transient experimental ischemic stroke in rats. Stroke induction was made by transient middle cerebral artery occlusion (tMCAO). 2 × 106 AD-MSCFGF1 was administrated intravenously 30 min after carotid reperfusion. The ability of technetium99m-hexamethyl propylene amine oxime (99mTc-HMPAO)-labeled AD-MSCFGF1 to enter into ischemic brain was evaluated 2 h post injection. 24 h post operation, the neurological recovery (rotarod and Roger's tests), the infarct volume (2, 3, 5-triphenyltetrazolium chloride, TTC assay), apoptosis rate (TUNEL assay), and the expression of FGF1 protein (western blotting) in the ischemic hemisphere were assessed. The 99mTc-HMPAO-labeled AD-MSCFGF1 could enter into the ischemic brain. Ischemic hemisphere activity was significantly higher than that observed in the contralateral hemisphere (p = 0.002). The administration of AD-MSCFGF1 resulted in significant improvement of neurological function tests and increased density of FGF1 protein in the peri-infarct area, while the infarct volume and the apoptotic index were significantly decreased, in comparison to the other treated groups. In conclusion, acute intravenous administration of AD-MSCFGF1 can be a novel and promising candidate approach for the treatment of ischemic stroke.


Assuntos
Fator 1 de Crescimento de Fibroblastos/genética , Infarto da Artéria Cerebral Média/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/terapia , Adipócitos/citologia , Adipócitos/metabolismo , Adipócitos/transplante , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Animais , Diferenciação Celular , Cérebro/metabolismo , Cérebro/patologia , Modelos Animais de Doenças , Fator 1 de Crescimento de Fibroblastos/metabolismo , Expressão Gênica , Humanos , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Infusões Intravenosas , Masculino , Células-Tronco Mesenquimais/citologia , Compostos Radiofarmacêuticos/administração & dosagem , Ratos , Ratos Wistar , Teste de Desempenho do Rota-Rod , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Tecnécio Tc 99m Exametazima/administração & dosagem , Transgenes
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