RESUMO
Bone marrow mesenchymal stem cells (MSC) have been tested and proven effective in some neurodegenerative diseases, but their tracking after transplantation may be challenging. Our group has previously demonstrated the feasibility and biosafety of rat MSC labeling with iron oxide superparamagnetic nanoparticles (SPION). In this study, we investigated the therapeutic potential of SPION-labeled MSC in a rat model of Huntington's disease, a genetic degenerative disease with characteristic deletion of striatal GABAergic neurons. MSC labeled with SPION were injected into the striatum 1h after quinolinic acid injection. FJ-C analysis demonstrated that MSC transplantation significantly decreased the number of degenerating neurons in the damaged striatum 7 days after lesion. In this period, MSC transplantation enhanced the striatal expression of FGF-2 but did not affect subventricular zone proliferation, as demonstrated by Ki67 proliferation assay. In addition, MSC transplantation significantly reduced the ventriculomegaly in the lesioned brain. MRI and histological techniques detected the presence of the SPION-labeled cells at the lesion site. SPION-labeled MSC produced magnetic resonance imaging (MRI) signals that were visible for at least 60 days after transplantation. Our data highlight the potential of adult MSC to reduce brain damage under neurodegenerative diseases and indicate the use of nanoparticles in cell tracking, supporting their potential as valuable tools for cell therapy.
Assuntos
Dextranos/uso terapêutico , Doença de Huntington/terapia , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Nanopartículas/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Ferrocianetos/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Doença de Huntington/patologia , Masculino , Células-Tronco Mesenquimais/citologia , Neostriado/efeitos dos fármacos , Neostriado/patologia , Degeneração Neural/patologia , Degeneração Neural/terapia , Ratos , Ratos Wistar , Coloração e RotulagemRESUMO
In this work, various ferro-ferricyanide oxidoreductase activities of rat liver mitochondria were studied to find conditions under which the outer membrane might restrict the flux of these highly charged non-biological anions. When the isotonic low ionic strength medium was supplemented with 25mM KCl, a several-fold increase in the succinate-ferricyanide reductase activity of mitochondria and in the rate of external NADH oxidation in the presence of ferrocyanide was observed. Mitochondrial respiration with 5mM ferrocyanide was almost completely inhibited after consumption of 3.8-18.5% of the dissolved oxygen, depending on the medium and the presence of 2,4-dinitrophenol. These and other experimental data together with mathematical modeling of the redox-state equilibrium suggest that the measured activities might be restricted by two factors: first, the permeability of the outer mitochondrial membrane and second, a strong influence of the ionic strength of incubation media on the intermembrane space redox reactions.