Efeitos do transplante autólogo de células-tronco mesenquimais em pacientes com Doença de Crohn refratária associada a fístulas perianais

Detalhes bibliográficos
Autor(a) principal: Luana Bernardi
Data de Publicação: 2021
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFMS
Texto Completo: https://repositorio.ufms.br/handle/123456789/3632
Resumo: Introduction: Crohn's disease (CD) is an inflammatory bowel disease, which is characterized by inflammation of the mucosa and perianal complications, such as fistulas, which can affect about one third of patients. Despite the existence of therapies to improve symptoms, some individuals do not respond to conventional medical treatments, requiring alternative therapies. In this context, cell therapy, through transplantation of mesenchymal stem cells (MSC) is promising for the control of the inflammatory process of perianal fistulas in refractory CD. Objective: We evaluated the efficacy and safety of autologous transplantation of adipose tissue-derived MSC in patients with refractory perianal fistulizing CD. Methods: Six adult patients were recruited, with a proven diagnosis of refractory perianal fistulizing CD, and the proposed intervention was three applications of MSC (1.6 x 106 cells / mL in each application). The cells were isolated from the adipose tissue, from the flanks, by liposuction and cultured with Dulbecco´s Modified Eagle´s Medium, fetal bovine serum and antibiotic / antimycotic. Before applications, the parameters of morphology, absence of contamination, viability, ability to adhere to the plastic surface, immunophenotyping and differentiation potential of the cells were analyzed. The evaluation of transplants occurred in the 12th and 24th weeks after the first application, considering aspects of safety and efficacy, which were compared to the data at the beginning of the intervention. Results: Three patients completed the study and MSC were inoculated in passages 4, 5 and 6 in eight fistulas in total. In four fistulas, the external opening was closed, with local re-epithelialization, two of which closed in the 12th week. However, in the 24th week, the pelvic MRI exam indicated improvement in only one of the patients. On the other hand, in the same period, the clinical index of activity of the perianal disease and the evaluation of the quality of life indicated progress for the three patients and, through the analysis of the simple endoscopic score of CD, two patients presented the endoscopically inactive disease to the end of follow-up. As for anthropometric measurements, most were shown to be adequate and the foods that had low consumption throughout the study, in accordance for the three evaluated, were those that belong to the group of beans. Conclusion: Autologous MSCs from adipose tissue have clinical potential to safely and safely treat perianal fistulas in refractory CD.
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spelling 2021-04-26T11:30:29Z2021-09-30T19:55:50Z2021https://repositorio.ufms.br/handle/123456789/3632Introduction: Crohn's disease (CD) is an inflammatory bowel disease, which is characterized by inflammation of the mucosa and perianal complications, such as fistulas, which can affect about one third of patients. Despite the existence of therapies to improve symptoms, some individuals do not respond to conventional medical treatments, requiring alternative therapies. In this context, cell therapy, through transplantation of mesenchymal stem cells (MSC) is promising for the control of the inflammatory process of perianal fistulas in refractory CD. Objective: We evaluated the efficacy and safety of autologous transplantation of adipose tissue-derived MSC in patients with refractory perianal fistulizing CD. Methods: Six adult patients were recruited, with a proven diagnosis of refractory perianal fistulizing CD, and the proposed intervention was three applications of MSC (1.6 x 106 cells / mL in each application). The cells were isolated from the adipose tissue, from the flanks, by liposuction and cultured with Dulbecco´s Modified Eagle´s Medium, fetal bovine serum and antibiotic / antimycotic. Before applications, the parameters of morphology, absence of contamination, viability, ability to adhere to the plastic surface, immunophenotyping and differentiation potential of the cells were analyzed. The evaluation of transplants occurred in the 12th and 24th weeks after the first application, considering aspects of safety and efficacy, which were compared to the data at the beginning of the intervention. Results: Three patients completed the study and MSC were inoculated in passages 4, 5 and 6 in eight fistulas in total. In four fistulas, the external opening was closed, with local re-epithelialization, two of which closed in the 12th week. However, in the 24th week, the pelvic MRI exam indicated improvement in only one of the patients. On the other hand, in the same period, the clinical index of activity of the perianal disease and the evaluation of the quality of life indicated progress for the three patients and, through the analysis of the simple endoscopic score of CD, two patients presented the endoscopically inactive disease to the end of follow-up. As for anthropometric measurements, most were shown to be adequate and the foods that had low consumption throughout the study, in accordance for the three evaluated, were those that belong to the group of beans. Conclusion: Autologous MSCs from adipose tissue have clinical potential to safely and safely treat perianal fistulas in refractory CD.Introdução: A doença de Crohn (DC) é uma doença inflamatória do intestino, que se caracteriza pela inflamação da mucosa e complicações perianais, como as fístulas, que podem afetar cerca de um terço dos pacientes. Apesar da existência de terapias para melhora dos sintomas, alguns indivíduos não respondem aos tratamentos médicos convencionais, necessitando de terapias alternativas. Neste contexto, a terapia celular, por meio do transplante de células-tronco mesenquimais (CTM) é promissora para o controle do processo inflamatório de fístulas perianais na DC refratária. Objetivo: Avaliou-se a eficácia e a segurança do transplante autólogo de CTM derivadas do tecido adiposo em pacientes com DC fistulizante perianal refratária. Métodos: Foram recrutados 6 pacientes adultos, com diagnóstico comprovado de DC fistulizante perianal refratária e a intervenção proposta foram três aplicações de CTM (1,6 x 106 células/mL em cada aplicação). As células foram isoladas do tecido adiposo, da região dos flancos, por lipoaspiração e cultivadas com meio Dulbecco´s Modified Eagle´s Medium, soro bovino fetal e antibiótico/antimicótico. Antes das aplicações, foram analisados os parâmetros de morfologia, ausência de contaminação, viabilidade, capacidade de aderência à superfície plástica, imunofenotipagem e potencial de diferenciação das células. A avaliação dos transplantes ocorreu na 12ª e 24ª semana após a primeira aplicação, considerando aspectos de segurança e de eficácia, que foram comparados aos dados do início da intervenção. Resultados: Três pacientes concluíram o estudo e foram inoculadas CTM nas passagens 4, 5 e 6 em oito fístulas no total. Em quatro fístulas ocorreu o fechamento da abertura externa, com reepitelização local, sendo que duas destas fecharam ainda na 12ª semana. No entanto, na 24ª semana o exame de ressonância magnética de pelve indicou melhora de somente um dos pacientes. Por outro lado, no mesmo período, o índice clínico de atividade da doença perianal e a avaliação da qualidade de vida indicaram progresso para os três pacientes e, por meio da análise do escore endoscópico simples da DC, dois pacientes apresentaram a doença endoscopicamente inativa ao final do acompanhamento. Quanto às medidas antropométricas, a maioria se mostrou adequada e os alimentos que tiveram baixo consumo ao longo do estudo, em conformidade para os três avaliados, foram aqueles que pertencem ao grupo dos feijões. Conclusão: As CTM autólogas do tecido adiposo apresentam potencial clínico parar tratar as fístulas perianais na DC refratária e de forma segura.Fundação Universidade Federal de Mato Grosso do SulUFMSBrasilDoença de Crohn. Células-tronco derivadas do tecido adiposo. 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dc.title.pt_BR.fl_str_mv Efeitos do transplante autólogo de células-tronco mesenquimais em pacientes com Doença de Crohn refratária associada a fístulas perianais
title Efeitos do transplante autólogo de células-tronco mesenquimais em pacientes com Doença de Crohn refratária associada a fístulas perianais
spellingShingle Efeitos do transplante autólogo de células-tronco mesenquimais em pacientes com Doença de Crohn refratária associada a fístulas perianais
Luana Bernardi
Doença de Crohn. Células-tronco derivadas do tecido adiposo. Transplante de células-tronco mesenquimais.
title_short Efeitos do transplante autólogo de células-tronco mesenquimais em pacientes com Doença de Crohn refratária associada a fístulas perianais
title_full Efeitos do transplante autólogo de células-tronco mesenquimais em pacientes com Doença de Crohn refratária associada a fístulas perianais
title_fullStr Efeitos do transplante autólogo de células-tronco mesenquimais em pacientes com Doença de Crohn refratária associada a fístulas perianais
title_full_unstemmed Efeitos do transplante autólogo de células-tronco mesenquimais em pacientes com Doença de Crohn refratária associada a fístulas perianais
title_sort Efeitos do transplante autólogo de células-tronco mesenquimais em pacientes com Doença de Crohn refratária associada a fístulas perianais
author Luana Bernardi
author_facet Luana Bernardi
author_role author
dc.contributor.advisor1.fl_str_mv Andreia Conceicao Milan Brochado Antoniolli da Silva
dc.contributor.author.fl_str_mv Luana Bernardi
contributor_str_mv Andreia Conceicao Milan Brochado Antoniolli da Silva
dc.subject.por.fl_str_mv Doença de Crohn. Células-tronco derivadas do tecido adiposo. Transplante de células-tronco mesenquimais.
topic Doença de Crohn. Células-tronco derivadas do tecido adiposo. Transplante de células-tronco mesenquimais.
description Introduction: Crohn's disease (CD) is an inflammatory bowel disease, which is characterized by inflammation of the mucosa and perianal complications, such as fistulas, which can affect about one third of patients. Despite the existence of therapies to improve symptoms, some individuals do not respond to conventional medical treatments, requiring alternative therapies. In this context, cell therapy, through transplantation of mesenchymal stem cells (MSC) is promising for the control of the inflammatory process of perianal fistulas in refractory CD. Objective: We evaluated the efficacy and safety of autologous transplantation of adipose tissue-derived MSC in patients with refractory perianal fistulizing CD. Methods: Six adult patients were recruited, with a proven diagnosis of refractory perianal fistulizing CD, and the proposed intervention was three applications of MSC (1.6 x 106 cells / mL in each application). The cells were isolated from the adipose tissue, from the flanks, by liposuction and cultured with Dulbecco´s Modified Eagle´s Medium, fetal bovine serum and antibiotic / antimycotic. Before applications, the parameters of morphology, absence of contamination, viability, ability to adhere to the plastic surface, immunophenotyping and differentiation potential of the cells were analyzed. The evaluation of transplants occurred in the 12th and 24th weeks after the first application, considering aspects of safety and efficacy, which were compared to the data at the beginning of the intervention. Results: Three patients completed the study and MSC were inoculated in passages 4, 5 and 6 in eight fistulas in total. In four fistulas, the external opening was closed, with local re-epithelialization, two of which closed in the 12th week. However, in the 24th week, the pelvic MRI exam indicated improvement in only one of the patients. On the other hand, in the same period, the clinical index of activity of the perianal disease and the evaluation of the quality of life indicated progress for the three patients and, through the analysis of the simple endoscopic score of CD, two patients presented the endoscopically inactive disease to the end of follow-up. As for anthropometric measurements, most were shown to be adequate and the foods that had low consumption throughout the study, in accordance for the three evaluated, were those that belong to the group of beans. Conclusion: Autologous MSCs from adipose tissue have clinical potential to safely and safely treat perianal fistulas in refractory CD.
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