RESUMO
We developed a viral vector Ad5/35-CAG-mBDNF expressing the mature form of BDNF (mBDNF). On the basis of olfactory ensheathing cells transduced with this adenovector, a new gene-cell construct was obtained. In experiments in vitro, high viability of the transduced olfactory ensheathing cells and enhanced secretion of BDNF by these cells were observed. It is possible that a new gene-cell construct will significantly increase the regenerative effects of transplanted olfactory ensheathing cells.
Assuntos
Mucosa Olfatória , Traumatismos da Medula Espinal , Fator Neurotrófico Derivado do Encéfalo , Vetores Genéticos/genética , Humanos , Regeneração Nervosa/genética , Bulbo Olfatório , Medula Espinal , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/terapiaRESUMO
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
Rat glioma cell line C6 expressing human poliovirus receptor (PVR) and susceptible to polioviruses (C6-PVR-BFP) was used to produce a clone with knockout of IFNα/ß (Ifnar1) receptor subunit 1 gene (Ifnar1). The sensitivity of C6-PVR-BFP cells to the vaccine strain of poliovirus type 3 (PV3) depended on the signaling pathways of the cell response to type 1 IFN. Using the model of subcutaneous tumor xenografts, we demonstrated oncolytic activity of PV3 against C6-PVR-BFP cells that depended on the expression of PVR and increased considerably upon disturbances in IFN response pathways.
Assuntos
Glioma/terapia , Glioma/virologia , Terapia Viral Oncolítica/métodos , Poliovirus/fisiologia , Animais , Linhagem Celular Tumoral , Glioma/metabolismo , Interferon-alfa/genética , Interferon beta/genética , Camundongos , Vírus Oncolíticos/fisiologia , Ratos , Ratos Mutantes , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/metabolismoRESUMO
Replicative ability of 5 oncolytic enterovirus strains was evaluated on a panel of 18 human normal and tumor cells. The capacity of each cell line to support replication of enterovirus strains varied. Cell lines weakly replicating one virus could be highly sensitive to another viral strain. Differences in the expression of CXADR cell receptor did not correlate with susceptibility to infection and replication of Coxsackie B virus, but complete inactivation of CXADR gene and poliovirus receptor gene (PVR) led to loss of the sensitivity to Coxsackie B5 and poliovirus, respectively. Detection of additional expression markers will contribute to understanding the causes of different sensitivity of tumor cells to viruses.
Assuntos
Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/metabolismo , Enterovirus/metabolismo , Enterovirus/patogenicidade , Vírus Oncolíticos/metabolismo , Vírus Oncolíticos/patogenicidade , Receptores Virais/metabolismo , Linhagem Celular Tumoral , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/genética , Enterovirus Humano B/metabolismo , Enterovirus Humano B/patogenicidade , Humanos , Receptores Virais/genética , Replicação Viral/genética , Replicação Viral/fisiologiaRESUMO
Metastatic prostate cancer is often associated with either primary or intractable castration-resistant prostate cancer (CRPC), thus justifying the search for entirely new ways of treatment. Oncolytic viruses are able to selectively induce the death of tumor cells without affecting normal cells. A murine Sendai virus has potential to be used as an oncolytic agent. However, tumors vary in their sensitivity to different viruses, prompting us to attempt to identify corresponding biomarkers that reflect the interaction of cancer cells and the virus. Here, we show that the sensitivity of primary prostatic adenocarcinoma cell lines to Sendai virus strain (SeVM) vary substantially. Using quantitative PCR, we evaluated expression levels of genes that encode RIG-1-like and Toll-like receptors (TLRs) in cell lines and showed that the levels of mRNAs that encode TLR3 and TLR7 correlate with a degree of sensitivity of the cells to Sendai virus. The lines with lower levels of TLR3 and TLR7 expression are more sensitive to the virus.
Assuntos
Vírus Oncolíticos , Neoplasias de Próstata Resistentes à Castração/terapia , Vírus Sendai , Animais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/genética , Receptor 3 Toll-Like/genética , Receptor 7 Toll-Like/genéticaRESUMO
A humanized line of rat C6 glioma cells expressing human poliovirus receptor was obtained and tested for the sensitivity to oncolytic effects of vaccine strains of type 1, 2, and 3 polioviruses. Presentation of the poliovirus receptor on the surface of C6 glioma cells was shown to be a necessary condition for the interaction of cells with polioviruses, but insufficient for complete poliovirus oncolysis.
