RESUMO
The translation of new therapies for spinal cord injury to clinical trials can be facilitated with large animal models close in morpho-physiological scale to humans. Here, we report functional restoration and morphological reorganization after spinal contusion in pigs, following a combined treatment of locomotor training facilitated with epidural electrical stimulation (EES) and cell-mediated triple gene therapy with umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial-derived neurotrophic factor, and neural cell adhesion molecule. Preliminary results obtained on a small sample of pigs 2 months after spinal contusion revealed the difference in post-traumatic spinal cord outcomes in control and treated animals. In treated pigs, motor performance was enabled by EES and the corresponding morpho-functional changes in hind limb skeletal muscles were accompanied by the reorganization of the glial cell, the reaction of stress cell, and synaptic proteins. Our data demonstrate effects of combined EES-facilitated motor training and cell-mediated triple gene therapy after spinal contusion in large animals, informing a background for further animal studies and clinical translation.
Assuntos
Terapia por Estimulação Elétrica , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Moléculas de Adesão de Célula Nervosa/genética , Traumatismos da Medula Espinal/terapia , Fator A de Crescimento do Endotélio Vascular/genética , Adenoviridae/genética , Animais , Terapia Baseada em Transplante de Células e Tecidos/métodos , Modelos Animais de Doenças , Espaço Epidural , Terapia Genética/métodos , Vetores Genéticos/uso terapêutico , Fator Neurotrófico Derivado de Linhagem de Célula Glial/uso terapêutico , Humanos , Atividade Motora/genética , Atividade Motora/fisiologia , Moléculas de Adesão de Célula Nervosa/uso terapêutico , Neuroglia/transplante , Recuperação de Função Fisiológica/genética , Recuperação de Função Fisiológica/efeitos da radiação , Medula Espinal/fisiopatologia , Medula Espinal/efeitos da radiação , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/fisiopatologia , Suínos/genética , Fator A de Crescimento do Endotélio Vascular/uso terapêuticoRESUMO
Transgenic insecticidal plants based on Bacillus thuringiensis (Bt) endotoxins, on proteinase inhibitors and on lectins, and transgenic herbicide tolerant plants are widely used in modern agriculture. The results of the studies on likelihood and non-likelihood of adverse effects of transgenic plants on the environment including: (i) effects on nontarget species; (ii) invasiveness; (iii) potential for transgenes to 'escape' into the environment by horizontal gene transfer; and (iv) adverse effects on soil biota are reviewed. In general, it seems that large-scale implementation of transgenic insecticidal and herbicide tolerant plants do not display considerable negative effects on the environments and, moreover, at least some transgenic plants can improve the corresponding environments and human health because their production considerably reduces the load of chemical insecticides and herbicides.