Uso de células-tronco mesenquimais no tratamento da sepse e da lesão pulmonar aguda
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da PUC_RS |
Texto Completo: | http://tede2.pucrs.br/tede2/handle/tede/7532 |
Resumo: | Mesenchymal stem cells (MSC) were first identified by Friedenstein and Petrakova (1966), who isolated these progenitor cells from rat bone marrow and found that these cells are able to differentiate into connective tissue lineage including bone, adipose tissue, cartilage and muscle. MSCs have emerged in recent years as therapeutic tools based on four important features: differentiation potential, capacity to modulate immune responses, pro-angiogenic and repair promoting capacities, and low immunogenicity, the latter feature may allow allogeneic treatments. Based on their immunomodulatory properties and paracrine effects through trophic factors with anti-fibrotic, anti-apoptotic or pro-angiogenic properties, MSCs are considered a promising instrument for cell therapy, in particular for inflammatory diseases. MSCs regulate the function of a broad range of immune cells, and are activated by inflammatory mediators released from activated immune cells. The mechanisms involved in the immunoregulatory activity of MSCs are still under investigation. Therefore, MSCs become a potential treatment alternative for sepsis and for acute lung infection, which may lead to the interruption of the sequence in the pathogenesis and cause mortality reduction of both pathologies. The principal objective of this study was to evaluate the therapeutic and immunomodulatory effect of MSCs in the treatment of sepsis and acute lung injury and search for their possible mechanisms of action. Our results demonstrated for the first time that the reduction of inflammation in sepsis caused by treatment with MSCs is directly involved in the inhibition of the pathway of mitogen-activated proteins (MAPKs) and that MSCs were unable to modulate the expression of toll-like receptors. During acute lung injury (ALI), the immunomodulation caused by the treatment and the decrease of the oxidative stress that consequently led to a decrease in the formation of extracellular neutrophil network (NETs), leading to an increase in the survival of animals with LPA. The promising results obtained in these studies are encouraging and suggest that MSCs might be a therapeutic option to treat sepsis and acute lung infection in patients in the future. |
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Oliveira, Jarbas Rodrigues de140.906.430-15http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4781448U1009.187.040-22http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4236705Z3Pedrazza, Leonardo2017-06-30T18:30:01Z2017-03-24http://tede2.pucrs.br/tede2/handle/tede/7532Mesenchymal stem cells (MSC) were first identified by Friedenstein and Petrakova (1966), who isolated these progenitor cells from rat bone marrow and found that these cells are able to differentiate into connective tissue lineage including bone, adipose tissue, cartilage and muscle. MSCs have emerged in recent years as therapeutic tools based on four important features: differentiation potential, capacity to modulate immune responses, pro-angiogenic and repair promoting capacities, and low immunogenicity, the latter feature may allow allogeneic treatments. Based on their immunomodulatory properties and paracrine effects through trophic factors with anti-fibrotic, anti-apoptotic or pro-angiogenic properties, MSCs are considered a promising instrument for cell therapy, in particular for inflammatory diseases. MSCs regulate the function of a broad range of immune cells, and are activated by inflammatory mediators released from activated immune cells. The mechanisms involved in the immunoregulatory activity of MSCs are still under investigation. Therefore, MSCs become a potential treatment alternative for sepsis and for acute lung infection, which may lead to the interruption of the sequence in the pathogenesis and cause mortality reduction of both pathologies. The principal objective of this study was to evaluate the therapeutic and immunomodulatory effect of MSCs in the treatment of sepsis and acute lung injury and search for their possible mechanisms of action. Our results demonstrated for the first time that the reduction of inflammation in sepsis caused by treatment with MSCs is directly involved in the inhibition of the pathway of mitogen-activated proteins (MAPKs) and that MSCs were unable to modulate the expression of toll-like receptors. During acute lung injury (ALI), the immunomodulation caused by the treatment and the decrease of the oxidative stress that consequently led to a decrease in the formation of extracellular neutrophil network (NETs), leading to an increase in the survival of animals with LPA. The promising results obtained in these studies are encouraging and suggest that MSCs might be a therapeutic option to treat sepsis and acute lung infection in patients in the future.As células-tronco mesenquimais (MSC) foram identificadas primeiramente por Friedenstein e Petrakova (1966), que isolaram estas células progenitoras a partir da medula óssea de rato e observaram serem capazes de se diferenciarem em linhagem de tecido conectivo, incluindo osso, tecido adiposo, cartilagem e músculo. As MSCs surgiram nos últimos anos como ferramentas terapêuticas baseadas em quatro características importantes: potencial de diferenciação, capacidade para modular a resposta imune, capacidades pró-angiogênicas promovendo regeneração tecidual, e baixa imunogenicidade, sendo que esta última característica pode permitir tratamentos alogênicos. Com base nas suas propriedades imunomoduladoras e efeitos parácrinos através de fatores tróficos com propriedades anti-fibróticas, anti-apoptóticas ou pró-angiogênicas, as MSCs são consideradas um instrumento promissor para a terapia celular, em particular para doenças inflamatórias. As MSCs regulam as funções de uma ampla gama de células imunes, e são ativadas por mediadores inflamatórios liberados de células imunes ativadas. Os mecanismos envolvidos na atividade imunorreguladora de MSCs estão ainda sob investigação. Desta forma, as células-tronco mesequimais se tornam uma potencial alternativa de tratamento para a sepse e para infecção pulmonar aguda, podendo levar a interrupção do curso da patogênese, e provocar a redução da mortalidade de ambas patologias. O principal objetivo deste trabalho foi avaliar o efeito terapêutico e imunomodulador de células-tronco mesenquimais no tratamento da sepse e da lesão pulmonar aguda e buscar os seus possíveis mecanismos de ação. Nossos resultados demonstraram pela primeira vez, que a redução da inflamação na sepse provocada pelo tratamento com células-tronco mesenquimais está diretamente envolvido a inibição da via das proteínas ativadas por mitógenos (MAPKs) e que as MSCs foram incapazes de modular a expressão de receptores do tipo toll. Durante a lesão pulmonar aguda (LPA) ficou evidente a imunomodulação provocada pelo tratamento e a diminuição do estresse oxidativo que consequentemente ocasionou a uma diminuição da formação das redes extracelulares de neutrófilos (NETs), levando a um aumento na sobrevida dos animais com LPA. Os resultados promissores obtidos neste estudo são encorajadores e sugerem que as MSCs podem ser uma opção terapêutica para tratar a sepse e a lesão pulmonar aguda em pacientes no futuro.Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-06-30T18:29:48Z No. of bitstreams: 1 TES_LEONARDO_PEDRAZZA_PARCIAL.pdf: 9312449 bytes, checksum: e82cef97eb17ae6eefdb30bc5fe133ed (MD5)Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-06-30T18:29:54Z (GMT) No. of bitstreams: 1 TES_LEONARDO_PEDRAZZA_PARCIAL.pdf: 9312449 bytes, checksum: e82cef97eb17ae6eefdb30bc5fe133ed (MD5)Made available in DSpace on 2017-06-30T18:30:01Z (GMT). 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dc.title.por.fl_str_mv |
Uso de células-tronco mesenquimais no tratamento da sepse e da lesão pulmonar aguda |
title |
Uso de células-tronco mesenquimais no tratamento da sepse e da lesão pulmonar aguda |
spellingShingle |
Uso de células-tronco mesenquimais no tratamento da sepse e da lesão pulmonar aguda Pedrazza, Leonardo Sepse Infecção Pulmonar Aguda Células-Tronco Mesenquimais Inflamação CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
title_short |
Uso de células-tronco mesenquimais no tratamento da sepse e da lesão pulmonar aguda |
title_full |
Uso de células-tronco mesenquimais no tratamento da sepse e da lesão pulmonar aguda |
title_fullStr |
Uso de células-tronco mesenquimais no tratamento da sepse e da lesão pulmonar aguda |
title_full_unstemmed |
Uso de células-tronco mesenquimais no tratamento da sepse e da lesão pulmonar aguda |
title_sort |
Uso de células-tronco mesenquimais no tratamento da sepse e da lesão pulmonar aguda |
author |
Pedrazza, Leonardo |
author_facet |
Pedrazza, Leonardo |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Oliveira, Jarbas Rodrigues de |
dc.contributor.advisor1ID.fl_str_mv |
140.906.430-15 |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4781448U1 |
dc.contributor.authorID.fl_str_mv |
009.187.040-22 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4236705Z3 |
dc.contributor.author.fl_str_mv |
Pedrazza, Leonardo |
contributor_str_mv |
Oliveira, Jarbas Rodrigues de |
dc.subject.por.fl_str_mv |
Sepse Infecção Pulmonar Aguda Células-Tronco Mesenquimais Inflamação |
topic |
Sepse Infecção Pulmonar Aguda Células-Tronco Mesenquimais Inflamação CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
description |
Mesenchymal stem cells (MSC) were first identified by Friedenstein and Petrakova (1966), who isolated these progenitor cells from rat bone marrow and found that these cells are able to differentiate into connective tissue lineage including bone, adipose tissue, cartilage and muscle. MSCs have emerged in recent years as therapeutic tools based on four important features: differentiation potential, capacity to modulate immune responses, pro-angiogenic and repair promoting capacities, and low immunogenicity, the latter feature may allow allogeneic treatments. Based on their immunomodulatory properties and paracrine effects through trophic factors with anti-fibrotic, anti-apoptotic or pro-angiogenic properties, MSCs are considered a promising instrument for cell therapy, in particular for inflammatory diseases. MSCs regulate the function of a broad range of immune cells, and are activated by inflammatory mediators released from activated immune cells. The mechanisms involved in the immunoregulatory activity of MSCs are still under investigation. Therefore, MSCs become a potential treatment alternative for sepsis and for acute lung infection, which may lead to the interruption of the sequence in the pathogenesis and cause mortality reduction of both pathologies. The principal objective of this study was to evaluate the therapeutic and immunomodulatory effect of MSCs in the treatment of sepsis and acute lung injury and search for their possible mechanisms of action. Our results demonstrated for the first time that the reduction of inflammation in sepsis caused by treatment with MSCs is directly involved in the inhibition of the pathway of mitogen-activated proteins (MAPKs) and that MSCs were unable to modulate the expression of toll-like receptors. During acute lung injury (ALI), the immunomodulation caused by the treatment and the decrease of the oxidative stress that consequently led to a decrease in the formation of extracellular neutrophil network (NETs), leading to an increase in the survival of animals with LPA. The promising results obtained in these studies are encouraging and suggest that MSCs might be a therapeutic option to treat sepsis and acute lung infection in patients in the future. |
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2017 |
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2017-06-30T18:30:01Z |
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2017-03-24 |
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