Avaliação do transplante alogênico de células tronco mesenquimais isoladas de tecido adiposo em cães portadores de sequela neurológica causada pela cinomose
Arquivos
Data
2017-08-25
Autores
Barros, Michele Andrade de 
Orientadores
Kerkis, Irina
Tipo
Tese de doutorado
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Resumo
Avaliar clinicamente a segurança e a eficácia terapêutica do transplante alogênico de Células Tronco Mesenquimais (CTM) de tecido adiposo canino em cães com sequelas neurológicas crônicas derivadas do vírus da cinomose. Métodos: Foram selecionados 20 cães com diagnóstico confirmado da doença e subsequente sequela neurológica com sinais mínimos de ataxia, paresia e ou plegia de membros torácicos e ou pélvicos, livres de formações neoplásicas, sem restrição de raça, sexo e com idades entre 6 a 125 meses. Foram realizados três transplantes de CTM alogênicas por via intravenosa em intervalos de 30 dias entre elas. O acompanhamento clínico geral foi realizado a cada 30 dias, incluindo-se foto e vídeo-documentação da evolução dos animais. As análises estatísticas utilizadas para comparar a classificação da resposta terapêutica entre as variáveis categóricas foram os testes Qui-Quadrado Simulado e Exato de Fisher, enquanto que para comparar as classificações da resposta terapêutica entre as variáveis numéricas foi utilizado o teste de Kruskal-Wallis. Resultados: 80% dos animais tratados apresentaram uma melhora do quadro neurológico e voltaram a deambular. Desses 80%, 50% apresentaram uma melhora significativa classificada como excelente (animal que voltou a deambular normalmente), 30% apresentaram melhora classificada como moderada (animal que voltou a deambular, porém com algum grau de dificuldade) e 20% apresentaram resposta classificada como leve (animal que apresentou uma pequena melhora neurológica, mas não voltou a deambular). De a cordo com a localização da lesão no SNC, 40% (N=8) tiveram lesão medular, 30% (N=6) lesão multifocal, 20% (N=4) lesão cerebelar e 10% (N=2) lesão tálamocortical (cortex cerebral). Seguindo uma análise de resposta terapêutica por localização da lesão no sistema nervoso, houve uma diferença significativa (valor – p= 0,005) entre os locais de lesão, sendo que 87,5% dos que tiveram lesão medular apresentaram uma resposta excelente, 75% dos que tiveram lesão cerebelar apresentaram resposta moderada, enquanto que 66,7% dos que tiveram lesão multifocal apresentaram resposta leve. Comparando os animais que receberam tratamento coadjuvante `a terapia com células-tronco (N=10), com os que só receberam terapia com células-tronco (N=10), não houve diferença significativa no tipo de resposta apresentada (valor –p= 0,703). Durante o tratamento, nenhum animal apresentou qualquer tipo de reação ou efeito colateral imediato ou tardio ao transplante alogênico. Conclusão: Múltiplas aplicações de Células Tronco Mesenquimais alogênicas derivadas de tecido adiposo canino mostraram-se seguras durante todo o acompanhamento em 100% dos animais tratados e eficazes em 80%, os quais voltaram a deambular. Os animais que possuem lesão exclusivamente medular, apresentam melhores chances de recuperar comparado aos animais com lesão neurológica multifocal.
Objectives: Clinically evaluate the safety and therapeutic efficacy of allogeneic mesenchymal stem cell transplantation (MTC) of canine adipose tissue in dogs with chronic neurological sequelae derived from the distemper virus. Methods: Twenty dogs with a confirmed diagnosis of the disease and subsequent neurological sequelae with minimal signs of ataxia, paresis and or folding of thoracic and or pelvic limbs, free of neoplastic formations, without restriction of race, sex, and between 6 and 125 months. Three allogeneic CTM transplants were performed intravenously at 30-day intervals between them. General clinical follow-up was performed every 30 days, including photo and video documentation of animal evolution. The KruskalWallis test was used to compare the classification of the therapeutic response among the categorical variables, using Chi-Square Simulated and Fisher's exact tests, while the Kruskal-Wallis test was used to compare the therapeutic response scores among the numerical variables. Results: 80% of the treated animals presented an improvement of the neurological picture and returned to ambulate. Of these 80%, 50% presented a significant improvement classified as excellent (an animal that returned to walk normally), 30% presented improvement classified as moderate (animal that returned to ambulate, but with some degree of difficulty) and 20% presented a response classified as mild (an animal that presented a slight neurological improvement, but did not go back to wandering). Of the patients with lesions in the CNS, 40% (N = 8) had spinal cord injury, 30% (N = 6) multifocal lesion, 20% (N = 4) cerebellar lesion and 10% thalamus-cortical (cerebral cortex). Following a therapeutic response analysis by location of lesion in the nervous system, there was a significant difference (p-value = 0.005) between lesion sites, with 87.5% of those with spinal cord lesion presenting an excellent response, 75% of who had a cerebellar lesion presented a moderate response, while 66.7% of those with a multifocal lesion presented a mild response. Comparing animals treated with stem cell therapy (N = 10) with only stem cell therapy (N = 10), there was no significant difference in the type of response presented (p-value = 0.703). During treatment, no animal presented any type of reaction or immediate or late side effect to allogeneic transplantation. Conclusion: Multiple applications of allogeneic mesenchymal stem cells derived from canine adipose tissue were shown to be safe during all follow-up in 100% of the treated and effective animals in 80%, who again wandered. The animals that have exclusively spinal cord lesions present a better chance of recovery compared to animals with multifocal neurological lesions.
Objectives: Clinically evaluate the safety and therapeutic efficacy of allogeneic mesenchymal stem cell transplantation (MTC) of canine adipose tissue in dogs with chronic neurological sequelae derived from the distemper virus. Methods: Twenty dogs with a confirmed diagnosis of the disease and subsequent neurological sequelae with minimal signs of ataxia, paresis and or folding of thoracic and or pelvic limbs, free of neoplastic formations, without restriction of race, sex, and between 6 and 125 months. Three allogeneic CTM transplants were performed intravenously at 30-day intervals between them. General clinical follow-up was performed every 30 days, including photo and video documentation of animal evolution. The KruskalWallis test was used to compare the classification of the therapeutic response among the categorical variables, using Chi-Square Simulated and Fisher's exact tests, while the Kruskal-Wallis test was used to compare the therapeutic response scores among the numerical variables. Results: 80% of the treated animals presented an improvement of the neurological picture and returned to ambulate. Of these 80%, 50% presented a significant improvement classified as excellent (an animal that returned to walk normally), 30% presented improvement classified as moderate (animal that returned to ambulate, but with some degree of difficulty) and 20% presented a response classified as mild (an animal that presented a slight neurological improvement, but did not go back to wandering). Of the patients with lesions in the CNS, 40% (N = 8) had spinal cord injury, 30% (N = 6) multifocal lesion, 20% (N = 4) cerebellar lesion and 10% thalamus-cortical (cerebral cortex). Following a therapeutic response analysis by location of lesion in the nervous system, there was a significant difference (p-value = 0.005) between lesion sites, with 87.5% of those with spinal cord lesion presenting an excellent response, 75% of who had a cerebellar lesion presented a moderate response, while 66.7% of those with a multifocal lesion presented a mild response. Comparing animals treated with stem cell therapy (N = 10) with only stem cell therapy (N = 10), there was no significant difference in the type of response presented (p-value = 0.703). During treatment, no animal presented any type of reaction or immediate or late side effect to allogeneic transplantation. Conclusion: Multiple applications of allogeneic mesenchymal stem cells derived from canine adipose tissue were shown to be safe during all follow-up in 100% of the treated and effective animals in 80%, who again wandered. The animals that have exclusively spinal cord lesions present a better chance of recovery compared to animals with multifocal neurological lesions.
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Citação
BARROS, Michele Andrade de. Avaliação do transplante alogênico de células tronco mesenquimais isoladas de tecido adiposo em cães portadores de sequela neurológica causada pela cinomose. São Paulo, 2017. Tese (Doutorado em Biologia estrutural e funcional) - Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, 2017.