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J Stroke Cerebrovasc Dis ; 27(9): 2453-2465, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30029838

RESUMO

INTRODUCTION: Stroke represents an attractive target for cell therapy. Although different types of cells have been employed in animal models with variable results, the human adipose-derived stem cells (hASCs) have demonstrated favorable characteristics in the treatment of diseases with inflammatory substrate, but experience in their intracerebral administration is lacking. The purpose of this study is to evaluate the effect and safety of the intracerebral application of hASCs in a stroke model. METHODS: A first group of Athymic Nude mice after stroke received a stereotactic injection of hASCs at a concentration of 4 × 104/µL at the penumbra area, a second group without stroke received the same cell concentration, and a third group had only stroke and no cells. After 7, 15, and 30 days, the animals underwent fluorodeoxyglucose-positron emission tomography and magnetic resonance imaging; subsequently, they were sacrificed for histological evaluation (HuNu, GFAP, IBA-1, Ki67, DCX) of the penumbra area and ipsilateral subventricular zone (iSVZ). RESULTS: The in vitro studies found no alterations in the molecular karyotype, clonogenic capacity, and expression of 62 kDa transcription factor and telomerase. Animals implanted with cells showed no adverse events. The implanted cells showed no evidence of proliferation or differentiation. However, there was an increase of capillaries, less astrocytes and microglia, and increased bromodeoxyuridine and doublecortin-positive cells in the iSVZ and in the vicinity of ischemic injury. CONCLUSIONS: These results suggest that hASCs in the implanted dose modulate inflammation, promote endogenous neurogenesis, and do not proliferate or migrate in the brain. These data confirm the safety of cell therapy with hASCs.


Assuntos
Isquemia Encefálica/terapia , Transplante de Células-Tronco , Tecido Adiposo/citologia , Animais , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Proliferação de Células , Modelos Animais de Doenças , Proteína Duplacortina , Gliose/diagnóstico por imagem , Gliose/metabolismo , Gliose/patologia , Gliose/terapia , Humanos , Masculino , Camundongos Nus , Microglia/metabolismo , Microglia/patologia , Atividade Motora , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Neovascularização Patológica/terapia , Neurônios/metabolismo , Neurônios/patologia , Distribuição Aleatória , Transplante de Células-Tronco/efeitos adversos , Células-Tronco/citologia , Transplante Heterólogo
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