RESUMO
This paper shows for the first time that co-transplantation of human olfactory ensheathing cells with neurotrophin-3 into spinal cord cysts is more effective for activation of remyelination than transplantation of cells with brain-derived neurotrophic factor and a combination of these two factors. The studied neurotrophic factors do not affect proliferation and migration of ensheathing cells in vitro. It can be concluded that the maximum improvement of motor function in rats receiving ensheathing cells with neurotrophin-3 is largely determined by activation of remyelination.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Neurotrofina 3 , Bulbo Olfatório , Remielinização , Animais , Ratos , Neurotrofina 3/metabolismo , Humanos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Remielinização/fisiologia , Bulbo Olfatório/citologia , Proliferação de Células , Medula Espinal/metabolismo , Bainha de Mielina/metabolismo , Bainha de Mielina/fisiologia , Células Cultivadas , Movimento Celular , Cistos/patologia , Feminino , Cistos do Sistema Nervoso Central/cirurgia , Cistos do Sistema Nervoso Central/patologiaRESUMO
A new gene-cell construct expressing nerve growth factor (NGF) has been developed. After obtaining engineered adenovectors Ad5-RGD-CAG-NGF and Ad5-RGD-CAG-EGFP, transduction efficiency and transgene expression were studied and multiplicity of infection was determined. The efficacy of transduced human olfactory ensheathing cells expressing NGF in restoring motor activity in rats has been shown in a limited period of time. Improved rat hindlimb mobility and cyst size reduction after gene-cell construct transplantation were more likely due to the cellular component of the construct.
Assuntos
Cistos , Vetores Genéticos , Fator de Crescimento Neural , Mucosa Olfatória , Animais , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Ratos , Mucosa Olfatória/metabolismo , Mucosa Olfatória/citologia , Humanos , Cistos/terapia , Cistos/genética , Cistos/patologia , Cistos/metabolismo , Vetores Genéticos/genética , Transdução Genética , Terapia Genética/métodos , Adenoviridae/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismoRESUMO
A gene-cell construct based on rat olfactory mucosa ensheathing cells transduced with an adenoviral vector encoding a mature form of brain neurotrophic factor (mBDNF) was transplanted into post-traumatic cysts of rat spinal cord. Transplantation of the gene-cell construct improved motor activity of the hind limbs and reduced the size of cysts in some animals. However, comparison of the effects of transduced and non-transduced ensheathing cells revealed no significant differences. In parallel in vitro experiments, a decrease in the proliferation of transduced cells compared to non-transduced cells was observed. It is likely that mBDNF reduces proliferation of transduced cells, which can affect their efficiency. The therapeutic efficacy of the new gene-cell construct is most likely provided by the cellular component.
Assuntos
Cistos , Traumatismos da Medula Espinal , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Cistos/genética , Cistos/terapia , Regeneração Nervosa , Mucosa Olfatória , Ratos , Recuperação de Função Fisiológica , Medula Espinal , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/terapiaRESUMO
Neurotrophin-3 enhances the effectiveness of human olfactory ensheathing cells in improving hind limb mobility in rats with post-traumatic cysts of the spinal cord. Transplantation of olfactory ensheathing cells into spinal cord cysts reduced their size; neurotrophin-3 did not modulate this effect. Combined preparation of human olfactory ensheathing cells and neurotrophin- 3 can be used in neurosurgery for the treatment of patients with spinal cord injuries.
Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Cistos , Neurotrofina 3 , Traumatismos da Medula Espinal , Animais , Transplante de Células , Cistos/terapia , Humanos , Fatores de Crescimento Neural/genética , Regeneração Nervosa , Neurotrofina 3/farmacologia , Ratos , Medula Espinal , Traumatismos da Medula Espinal/terapiaRESUMO
We studied the efficiency of transplantation of neural stem/progenitor cells from human olfactory mucosa in chronic spinal cord injury. Neural stem/progenitor cells were obtained by a protocol modified by us and transplanted to rats with spinal post-traumatic cysts. It was shown that transplantation of neural stem/progenitor cells from human olfactory lining improved motor activity of hind limbs in the recipient rat with spinal post-traumatic cysts (according to BBB scale).
Assuntos
Atividade Motora/fisiologia , Células-Tronco Neurais/transplante , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/terapia , Transplante de Células-Tronco , Animais , Doença Crônica , Membro Posterior , Humanos , Cavidade Nasal/citologia , Cavidade Nasal/cirurgia , Células-Tronco Neurais/citologia , Células-Tronco Neurais/fisiologia , Mucosa Olfatória/citologia , Mucosa Olfatória/cirurgia , Cultura Primária de Células , Ratos , Ratos Wistar , Medula Espinal/cirurgia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/cirurgia , Transplante HeterólogoRESUMO
In experiments on rats, co-transplantation of olfactory ensheathing cells of the human olfactory mucosa and neural stem/progenitor cells from the same source into post-traumatic cysts of the spinal cord led to improvement of the motor activity of the hind limbs and reduced the size of the cysts in some animals by 4-12%. The transplantation of a combination of the olfactory mucosa cells is effective and can be used in preclinical trials for the treatment of spinal cord injuries.
Assuntos
Cistos/terapia , Células Epiteliais/transplante , Células-Tronco Neurais/transplante , Recuperação de Função Fisiológica/fisiologia , Esferoides Celulares/transplante , Traumatismos da Medula Espinal/terapia , Animais , Terapia Baseada em Transplante de Células e Tecidos/métodos , Cistos/patologia , Cistos/fisiopatologia , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Feminino , Humanos , Atividade Motora/fisiologia , Células-Tronco Neurais/citologia , Células-Tronco Neurais/fisiologia , Mucosa Olfatória/citologia , Mucosa Olfatória/fisiologia , Cultura Primária de Células , Ratos , Ratos Wistar , Esferoides Celulares/citologia , Esferoides Celulares/fisiologia , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Transplante Heterólogo , Resultado do TratamentoRESUMO
We studied survival of rat ensheathing cells after transplantation into experimental posttraumatic cysts. These cells were prepared according to our original protocol, labeled with intravital membrane dye PKH26, and transplanted into posttraumatic cysts of the spinal cord. The presence of cysts was verified by magnetic resonance imaging. Olfactory ensheathing cells were detected in the spinal cord by the immunofluorescence method. It was shown that rat olfactory ensheathing cells survived in the spinal cord over 4 weeks and their migration was observed. High survival rate and the possibility of obtaining olfactory ensheathing cells from the olfactory mucosa of patients for creation of an autologous preparation allow considering them as very promising material for the treatment of patients with posttraumatic cysts of the spinal cord.
Assuntos
Cistos/terapia , Mucosa Olfatória/citologia , Traumatismos da Medula Espinal/terapia , Animais , Sobrevivência Celular/fisiologia , Terapia Baseada em Transplante de Células e Tecidos , Regeneração Nervosa/fisiologia , RatosRESUMO
We studied the possibility of using BSA-coated magnetic iron oxide nanoparticles for magnetic resonance imaging diagnosis of C6 glioblastoma, 4T1 mammary adenocarcinoma, and RS-1 hepatic mucous carcinoma. In all three cases, magnetic nanoparticles accumulated in the tumor and its large vessels. Magnetic resonance imaging with contrast agent allows visualization of the tumor tissue and its vascularization.
Assuntos
Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Meios de Contraste/farmacocinética , Glioma/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Nanopartículas de Magnetita/administração & dosagem , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Adenocarcinoma/metabolismo , Adenocarcinoma Mucinoso/metabolismo , Animais , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Meios de Contraste/química , Feminino , Compostos Férricos/administração & dosagem , Compostos Férricos/química , Glioma/metabolismo , Injeções Subcutâneas , Neoplasias Hepáticas/metabolismo , Imageamento por Ressonância Magnética/métodos , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos WistarRESUMO
BSA-coated Fe3O4 nanoparticles with different hydrodynamic diameters (36±4 and 85±10 nm) were synthesized, zeta potential and T2 relaxivity were determined, and their morphology was studied by transmission electron microscopy. Studies on rats with experimental glioma C6 showed that smaller nanoparticles more effectively accumulated in the tumor and circulated longer in brain vessels. Optimization of the hydrodynamic diameter improves the efficiency of MRT contrast agent.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Meios de Contraste/química , Glioma/diagnóstico por imagem , Nanopartículas de Magnetita/química , Animais , Animais não Endogâmicos , Linhagem Celular Tumoral , Meios de Contraste/farmacocinética , Feminino , Imageamento por Ressonância Magnética , Microscopia Eletrônica de Transmissão , Transplante de Neoplasias , Tamanho da Partícula , Soroalbumina Bovina/químicaRESUMO
HYPOTHESIS: Hydrophobic bacteriochlorin based photosensitizer (PS) can be effectively immobilized on MNP covered by human serum albumin (HSA). PS loading into MNP protein shell allows solubilizing PS in water solution without altering its photodynamic activity. MNP@PS can serve as diagnostic tool for tracking PS delivery to tumor tissues by MRI. EXPERIMENTS: Immobilization on MNP-HSA-PEG was performed by adding PS solution in organic solvents with further purification. MNP@PS were characterized by DLS, HAADF STEM and AFM. Absorbance and fluorescence measurements were used to assess PS photophysical properties before and after immobilization. MNP@PS internalization into CT26 cells was investigated by confocal microscopy in vitro and MRI/IVIS were used for tracking MNP@PS delivery to tumors in vivo. FINDINGS: MNP@PS complexes were stable in water solution and retained PS photophysical activity. The length of side chain affected MNP@PS size, loading capacity and cell internalization. In vitro testing demonstrated MNP@PS delivery to cancer cells followed by photoinduced toxicity. In vivo studies confirmed that as-synthetized complexes can be used for MRI tracking over drug accumulation in tumors.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/química , Fármacos Fotossensibilizantes/administração & dosagem , Porfirinas/administração & dosagem , Animais , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas de Magnetita/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Albumina Sérica Humana/química , Propriedades de SuperfícieRESUMO
Correction for 'New ferrocene-based 2-thio-imidazol-4-ones and their copper complexes. Synthesis and cytotoxicity' by D. A. Guk et al., Dalton Trans., 2018, DOI: 10.1039/c8dt03164a.
RESUMO
Synthesis, characterization (HRMS, NMR, EPR, XANES, UV-Vis spectroscopy, and electrochemistry), DNA and BSA binding and in vitro biological screening of two new ferrocene-incorporated thiohydantoin derivatives (5 and 6) and their copper coordination compounds are reported. The ferrocene-based thiohydantoin derivatives were prepared by copper-catalyzed azide alkyne cycloaddition reactions between alkynyl ferrocenes and 5-(Z)-3-(2-azidoethyl)-2-(methylthio)-5-(pyridin-2-ylmethylene)-1H-imidazol-4H-one. Alkynyl ferrocenes necessary for these syntheses were prepared by new procedures. Intermolecular redox reactions between the ferrocene fragment and copper(+2) coordinated ions were studied by different methods to determine the mechanism and kinetic constants of redox processes. Ferrocene-containing imidazolones (5 and 6) and their copper complexes were also tested for their in vitro cytotoxic activity against MCF-7 and A-549 carcinoma cells, and also against the noncancerous cell line Hek-293. The results showed modest cytotoxicity against the subjected cancer cell line compared with cisplatin. The ability of the obtained compounds to cause DNA degradation and cell apoptosis was investigated, and the distribution of cytosol/pellets was studied by AAS.