Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/30596
Title: IGF-1-Overexpressing Mesenchymal Stem/Stromal Cells Promote Immunomodulatory and Proregenerative Effects in Chronic Experimental Chagas Disease
Authors: Silva, Daniela Nascimento
Souza, Bruno Solano de Freitas
Azevedo, Carine Machado
Vasconcelos, Juliana Fraga
Jesus, Paloma Gomes de
Feitoza, Malena Sebastiana Barreto
Meira, Cassio Santana
Carvalho, Gisele B
Cavalcante, Bruno Raphael Ribeiro
Santos, Ricardo Ribeiro dos
Soares, Milena Botelho Pereira
Affilliation: Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
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.
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
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.
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.
Abstract: Mesenchymal stem/stromal cells (MSCs) have been investigated for the treatment of diseases that affect the cardiovascular system, including Chagas disease. MSCs are able to promote their beneficial actions through the secretion of proregenerative and immunomodulatory factors, including insulin-like growth factor-1 (IGF-1), which has proregenerative actions in the heart and skeletal muscle. Here, we evaluated the therapeutic potential of IGF-1-overexpressing MSCs (MSC_IGF-1) in a mouse model of chronic Chagas disease. C57BL/6 mice were infected with Colombian strain Trypanosoma cruzi and treated with MSCs, MSC_IGF-1, or vehicle (saline) six months after infection. RT-qPCR analysis confirmed the presence of transplanted cells in both the heart and skeletal muscle tissues. Transplantation of either MSCs or MSC_IGF-1 reduced the number of inflammatory cells in the heart when compared to saline controls. Moreover, treatment with MSCs or MSC_IGF-1 significantly reduced TNF-α, but only MSC treatment reduced IFN-γ production compared to the saline group. Skeletal muscle sections of both MSC- and MSC_IGF-1-treated mice showed a reduction in fibrosis compared to saline controls. Importantly, the myofiber area was reduced in T. cruzi-infected mice, and this was recovered after treatment with MSC_IGF-1. Gene expression analysis in the skeletal muscle showed a higher expression of pro- and anti-inflammatory molecules in MSC_IGF-1-treated mice compared to MSCs alone, which significantly reduced the expression of TNF-α and IL-1β. In conclusion, our results indicate the therapeutic potential of MSC_IGF-1, with combined immunomodulatory and proregenerative actions to the cardiac and skeletal muscles.
Keywords: Stem Cells
Mesenchymal Cells
Chagas disease
Stromal cells
Cardiovascular System
Stem Cell Transplantation
Myocardium
Muscle, Skeletal
keywords: Células tronco
Células Mesenquimais
Doença de Chagas
Células estaminais
Sistema cardiovascular
Transplante de células-tronco
Musculo cardíaco
Musculo esquelético
Issue Date: 2018
Publisher: Hindawi Publishing Corporation
Citation: SILVA, D. N. et al. IGF-1-Overexpressing Mesenchymal Stem/Stromal Cells Promote Immunomodulatory and Proregenerative Effects in Chronic Experimental Chagas Disease. Stem Cells International, ID 9108681, 2018.
DOI: 10.1155/2018/9108681
ISSN: 1687-966X
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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