Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/28172 |
Resumo: | FINEP, CNPq, and FAPESB for research funding. |
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Silva, Daniela NascimentoSouza, Bruno Solano de FreitasVasconcelos, Juliana FragaAzevedo, Carine MachadoValim, Clarissa Xavier ResendeParedes, Bruno DiazRocha, Vinicius Pinto CostaCarvalho, Gisele BatistaDaltro, Pamela SantanaMacambira, Simone GarciaNonaka, Carolina Kymie VasquesSantos, Ricardo Ribeiro dosSoares, Milena Botelho Pereira2018-08-16T12:47:51Z2018-08-16T12:47:51Z2018SILVA, D. N. et al. Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy. Frontiers in Immunology, v. 9, art. 1449, 2018.1664-3224https://www.arca.fiocruz.br/handle/icict/2817210.3389/fimmu.2018.01449FINEP, CNPq, and FAPESB for research funding.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science and Technology for Regenerative Medicine. Rio de Janeiro, RJ, BrazilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / National Institute of Science and Technology for Regenerative Medicine. Rio de Janeiro, RJ, BrazilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / National Institute of Science and Technology for Regenerative Medicine. Rio de Janeiro, RJ, BrazilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science and Technology for Regenerative Medicine. Rio de Janeiro, RJ, BrazilGenetic modification of mesenchymal stem cells (MSCs) is a promising strategy to improve their therapeutic effects. Granulocyte-colony stimulating factor (G-CSF) is a growth factor widely used in the clinical practice with known regenerative and immunomodulatory actions, including the mobilization of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Here we evaluated the therapeutic potential of MSCs overexpressing G-CSF (MSC_G-CSF) in a model of inflammatory cardiomyopathy due to chronic Chagas disease. C57BL/6 mice were treated with wild-type MSCs, MSC_G-CSF, or vehicle (saline) 6 months after infection with Trypanosoma cruzi. Transplantation of MSC_G-CSF caused an increase in the number of circulating leukocytes compared to wild-type MSCs. Moreover, G-CSF overexpression caused an increase in migration capacity of MSCs to the hearts of infected mice. Transplantation of either MSCs or MSC_G-CSF improved exercise capacity, when compared to saline-treated chagasic mice. MSC_G-CSF mice, however, were more potent than MSCs in reducing the number of infiltrating leukocytes and fibrosis in the heart. Similarly, MSC_G-CSF-treated mice presented significantly lower levels of inflammatory mediators, such as IFNγ, TNFα, and Tbet, with increased IL-10 production. A marked increase in the percentage of Tregs and MDSCs in the hearts of infected mice was seen after administration of MSC_G-CSF, but not MSCs. Moreover, Tregs were positive for IL-10 in the hearts of T. cruzi-infected mice. In vitro analysis showed that recombinant hG-CSF and conditioned medium of MSC_G-CSF, but not wild-type MSCs, induce chemoattraction of MDSCs in a transwell assay. Finally, MDSCs purified from hearts of MSC_G-CSF transplanted mice inhibited the proliferation of activated splenocytes in a co-culture assay. Our results demonstrate that G-CSF overexpression by MSCs potentiates their immunomodulatory effects in our model of Chagas disease and suggest that mobilization of suppressor cell populations such as Tregs and MDSCs as a promising strategy for the treatment of chronic Chagas disease. Finally, our results reinforce the therapeutic potential of genetic modification of MSCs, aiming at increasing their paracrine actions.engFrontiers MediaCélulas-tronco mesenquimaisFator estimulador de colônias de granulócitosImunomodulaçãoDoença de ChagasCardiomiopatiaMesenchymal stem cellsGranulocyte-colony stimulating factorImmunomodulationChagas diseaseCardiomyopathyGranulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/28172/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSilva DN Granulocyte-Colony Stimulating 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| dc.title.pt_BR.fl_str_mv |
Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy |
| title |
Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy |
| spellingShingle |
Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy Silva, Daniela Nascimento Células-tronco mesenquimais Fator estimulador de colônias de granulócitos Imunomodulação Doença de Chagas Cardiomiopatia Mesenchymal stem cells Granulocyte-colony stimulating factor Immunomodulation Chagas disease Cardiomyopathy |
| title_short |
Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy |
| title_full |
Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy |
| title_fullStr |
Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy |
| title_full_unstemmed |
Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy |
| title_sort |
Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy |
| author |
Silva, Daniela Nascimento |
| author_facet |
Silva, Daniela Nascimento Souza, Bruno Solano de Freitas Vasconcelos, Juliana Fraga Azevedo, Carine Machado Valim, Clarissa Xavier Resende Paredes, Bruno Diaz Rocha, Vinicius Pinto Costa Carvalho, Gisele Batista Daltro, Pamela Santana Macambira, Simone Garcia Nonaka, Carolina Kymie Vasques Santos, Ricardo Ribeiro dos Soares, Milena Botelho Pereira |
| author_role |
author |
| author2 |
Souza, Bruno Solano de Freitas Vasconcelos, Juliana Fraga Azevedo, Carine Machado Valim, Clarissa Xavier Resende Paredes, Bruno Diaz Rocha, Vinicius Pinto Costa Carvalho, Gisele Batista Daltro, Pamela Santana Macambira, Simone Garcia Nonaka, Carolina Kymie Vasques Santos, Ricardo Ribeiro dos Soares, Milena Botelho Pereira |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Silva, Daniela Nascimento Souza, Bruno Solano de Freitas Vasconcelos, Juliana Fraga Azevedo, Carine Machado Valim, Clarissa Xavier Resende Paredes, Bruno Diaz Rocha, Vinicius Pinto Costa Carvalho, Gisele Batista Daltro, Pamela Santana Macambira, Simone Garcia Nonaka, Carolina Kymie Vasques Santos, Ricardo Ribeiro dos Soares, Milena Botelho Pereira |
| dc.subject.other.pt_BR.fl_str_mv |
Células-tronco mesenquimais Fator estimulador de colônias de granulócitos Imunomodulação Doença de Chagas Cardiomiopatia |
| topic |
Células-tronco mesenquimais Fator estimulador de colônias de granulócitos Imunomodulação Doença de Chagas Cardiomiopatia Mesenchymal stem cells Granulocyte-colony stimulating factor Immunomodulation Chagas disease Cardiomyopathy |
| dc.subject.en.pt_BR.fl_str_mv |
Mesenchymal stem cells Granulocyte-colony stimulating factor Immunomodulation Chagas disease Cardiomyopathy |
| description |
FINEP, CNPq, and FAPESB for research funding. |
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2018 |
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2018-08-16T12:47:51Z |
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2018-08-16T12:47:51Z |
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2018 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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SILVA, D. N. et al. Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy. Frontiers in Immunology, v. 9, art. 1449, 2018. |
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https://www.arca.fiocruz.br/handle/icict/28172 |
| dc.identifier.issn.pt_BR.fl_str_mv |
1664-3224 |
| dc.identifier.doi.none.fl_str_mv |
10.3389/fimmu.2018.01449 |
| identifier_str_mv |
SILVA, D. N. et al. Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy. Frontiers in Immunology, v. 9, art. 1449, 2018. 1664-3224 10.3389/fimmu.2018.01449 |
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Frontiers Media |
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Frontiers Media |
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