| Author | Silva, Daniela Nascimento | |
| Author | Souza, Bruno Solano de Freitas | |
| Author | Vasconcelos, Juliana Fraga | |
| Author | Azevedo, Carine Machado | |
| Author | Valim, Clarissa Xavier Resende | |
| Author | Paredes, Bruno Diaz | |
| Author | Rocha, Vinicius Pinto Costa | |
| Author | Carvalho, Gisele Batista | |
| Author | Daltro, Pamela Santana | |
| Author | Macambira, Simone Garcia | |
| Author | Nonaka, Carolina Kymie Vasques | |
| Author | Santos, Ricardo Ribeiro dos | |
| Author | Soares, Milena Botelho Pereira | |
| Access date | 2018-08-16T12:47:51Z | |
| Available date | 2018-08-16T12:47:51Z | |
| Document date | 2018 | |
| Citation | 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. | pt_BR |
| ISSN | 1664-3224 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/28172 | |
| Sponsorship | FINEP, CNPq, and FAPESB for research funding. | pt_BR |
| Language | eng | pt_BR |
| Publisher | Frontiers Media | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | Células-tronco mesenquimais | pt_BR |
| Subject in Portuguese | Fator estimulador de colônias de granulócitos | pt_BR |
| Subject in Portuguese | Imunomodulação | pt_BR |
| Subject in Portuguese | Doença de Chagas | pt_BR |
| Subject in Portuguese | Cardiomiopatia | pt_BR |
| Title | Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.3389/fimmu.2018.01449 | |
| Abstract | Genetic 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. | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | Hospital 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, Brazil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / National Institute of Science and Technology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / National Institute of Science and Technology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil | pt_BR |
| Affilliation | Hospital 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, Brazil | pt_BR |
| Subject | Mesenchymal stem cells | pt_BR |
| Subject | Granulocyte-colony stimulating factor | pt_BR |
| Subject | Immunomodulation | pt_BR |
| Subject | Chagas disease | pt_BR |
| Subject | Cardiomyopathy | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
