IGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injury
Autor(a) principal: | |
---|---|
Data de Publicação: | 2019 |
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/34630 |
Resumo: | Brazilian agencies: The National Bank for Economic and Social Development (BNDES), the National Research Council (CNPq), the Foundation of Support for Research of the State of Bahia (FAPESB) and Funding Authority for Studies and Projects (FINEP). |
id |
CRUZ_363b8b07979261866e418121837a0f29 |
---|---|
oai_identifier_str |
oai:www.arca.fiocruz.br:icict/34630 |
network_acronym_str |
CRUZ |
network_name_str |
Repositório Institucional da FIOCRUZ (ARCA) |
repository_id_str |
2135 |
spelling |
Allahdadi, Kyan JamesSantana, Thaís Alves deSantos, Girlaine CaféAzevedo, Carine MachadoMota, Roberta AlvesNonaka, Carolina KymieSilva, Daniela NascimentoValim, Clarissa Xavier ResendeFigueira, Cláudio PereiradosSantos, Washington Luis ConradoEspirito Santo, Renan Fernandes doEvangelista, Afrânio FerreiraVillarreal, Cristiane FloraSantos, Ricardo Ribeiro dosSouza, Bruno Solano Freitas deSoares, Milena Botelho Pereira2019-08-06T17:35:12Z2019-08-06T17:35:12Z2019ALLAHDADI, Kyan James et al. IGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injury. Stem Cell Research & Therapy, v. 10, p. 1-14, 2019.1757-6512https://www.arca.fiocruz.br/handle/icict/3463010.1186/s13287-019-1223-zBrazilian agencies: The National Bank for Economic and Social Development (BNDES), the National Research Council (CNPq), the Foundation of Support for Research of the State of Bahia (FAPESB) and Funding Authority for Studies and Projects (FINEP).Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brasil / São Rafael Hospital. D’Or Institute for Research and Education. Salvador, BA, Brazil.Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil.Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil.Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil.Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / São Rafael Hospital. D’Or Institute for Research and Education. Salvador, BA, Brazil.Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil.Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brasil / National Institute of Science and Technology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil.Hospital São Rafael. Center for Biotechnology and Cell Therapy. 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 / São Rafael Hospital. D’Or Institute for Research and Education. Salvador, BA, Brazil.Hospital São Rafael. Center for Biotechnology and Cell Therapy. 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.Survival and therapeutic actions of bone marrow-derived mesenchymal stem cells (BMMSCs) can be limited by the hostile microenvironment present during acute spinal cord injury (SCI). Here, we investigated whether BMMSCs overexpressing insulin-like growth factor 1 (IGF-1), a cytokine involved in neural development and injury repair, improved the therapeutic effects of BMMSCs in SCI. Methods: Using a SCI contusion model in C57Bl/6 mice, we transplanted IGF-1 overexpressing or wild-type BMMSCs into the lesion site following SCI and evaluated cell survival, proliferation, immunomodulation, oxidative stress, myelination, and functional outcomes. Results: BMMSC-IGF1 transplantation was associated with increased cell survival and recruitment of endogenous neural progenitor cells compared to BMMSC- or saline-treated controls. Modulation of gene expression of pro- and anti-inflammatory mediators was observed after BMMSC-IGF1 and compared to saline- and BMMSC-treated mice. Treatment with BMMSC-IGF1 restored spinal cord redox homeostasis by upregulating antioxidant defense genes. BMMSC-IGF1 protected against SCI-induced myelin loss, showing more compact myelin 28 days after SCI. Functional analyses demonstrated significant gains in BMS score and gait analysis in BMMSC-IGF1, compared to BMMSC or saline treatment. Conclusions: Overexpression of IGF-1 in BMMSC resulted in increased cell survival, immunomodulation, myelination, and functional improvements, suggesting that IGF-1 facilitates the regenerative actions of BMMSC in acute SCI.engBMCLesão medularCélulas-tronco mesenquimais derivadas da medula ósseaIGF-1Terapia gênica e celularSpinal cord injuryBone marrow-derived mesenchymal stem cellsIGF-1Gene and cell therapyIGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injuryinfo: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/34630/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALAllahdadi, K.J. IGF- 1 overexpression improves...2019.pdfAllahdadi, K.J. IGF- 1 overexpression improves...2019.pdfapplication/pdf9606598https://www.arca.fiocruz.br/bitstream/icict/34630/2/Allahdadi%2c%20K.J.%20IGF-%201%20overexpression%20improves...2019.pdfc2b7884b1d5910a32ab4890d450f15b8MD52TEXTAllahdadi, K.J. IGF- 1 overexpression improves...2019.pdf.txtAllahdadi, K.J. IGF- 1 overexpression improves...2019.pdf.txtExtracted texttext/plain50841https://www.arca.fiocruz.br/bitstream/icict/34630/3/Allahdadi%2c%20K.J.%20IGF-%201%20overexpression%20improves...2019.pdf.txt183080281fe4c9a345e987c3f7360198MD53icict/346302023-03-15 14:34:18.167oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:34:18Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
dc.title.pt_BR.fl_str_mv |
IGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injury |
title |
IGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injury |
spellingShingle |
IGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injury Allahdadi, Kyan James Lesão medular Células-tronco mesenquimais derivadas da medula óssea IGF-1 Terapia gênica e celular Spinal cord injury Bone marrow-derived mesenchymal stem cells IGF-1 Gene and cell therapy |
title_short |
IGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injury |
title_full |
IGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injury |
title_fullStr |
IGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injury |
title_full_unstemmed |
IGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injury |
title_sort |
IGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injury |
author |
Allahdadi, Kyan James |
author_facet |
Allahdadi, Kyan James Santana, Thaís Alves de Santos, Girlaine Café Azevedo, Carine Machado Mota, Roberta Alves Nonaka, Carolina Kymie Silva, Daniela Nascimento Valim, Clarissa Xavier Resende Figueira, Cláudio Pereira dosSantos, Washington Luis Conrado Espirito Santo, Renan Fernandes do Evangelista, Afrânio Ferreira Villarreal, Cristiane Flora Santos, Ricardo Ribeiro dos Souza, Bruno Solano Freitas de Soares, Milena Botelho Pereira |
author_role |
author |
author2 |
Santana, Thaís Alves de Santos, Girlaine Café Azevedo, Carine Machado Mota, Roberta Alves Nonaka, Carolina Kymie Silva, Daniela Nascimento Valim, Clarissa Xavier Resende Figueira, Cláudio Pereira dosSantos, Washington Luis Conrado Espirito Santo, Renan Fernandes do Evangelista, Afrânio Ferreira Villarreal, Cristiane Flora Santos, Ricardo Ribeiro dos Souza, Bruno Solano Freitas de Soares, Milena Botelho Pereira |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Allahdadi, Kyan James Santana, Thaís Alves de Santos, Girlaine Café Azevedo, Carine Machado Mota, Roberta Alves Nonaka, Carolina Kymie Silva, Daniela Nascimento Valim, Clarissa Xavier Resende Figueira, Cláudio Pereira dosSantos, Washington Luis Conrado Espirito Santo, Renan Fernandes do Evangelista, Afrânio Ferreira Villarreal, Cristiane Flora Santos, Ricardo Ribeiro dos Souza, Bruno Solano Freitas de Soares, Milena Botelho Pereira |
dc.subject.other.pt_BR.fl_str_mv |
Lesão medular Células-tronco mesenquimais derivadas da medula óssea IGF-1 Terapia gênica e celular |
topic |
Lesão medular Células-tronco mesenquimais derivadas da medula óssea IGF-1 Terapia gênica e celular Spinal cord injury Bone marrow-derived mesenchymal stem cells IGF-1 Gene and cell therapy |
dc.subject.en.pt_BR.fl_str_mv |
Spinal cord injury Bone marrow-derived mesenchymal stem cells IGF-1 Gene and cell therapy |
description |
Brazilian agencies: The National Bank for Economic and Social Development (BNDES), the National Research Council (CNPq), the Foundation of Support for Research of the State of Bahia (FAPESB) and Funding Authority for Studies and Projects (FINEP). |
publishDate |
2019 |
dc.date.accessioned.fl_str_mv |
2019-08-06T17:35:12Z |
dc.date.available.fl_str_mv |
2019-08-06T17:35:12Z |
dc.date.issued.fl_str_mv |
2019 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
ALLAHDADI, Kyan James et al. IGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injury. Stem Cell Research & Therapy, v. 10, p. 1-14, 2019. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/34630 |
dc.identifier.issn.pt_BR.fl_str_mv |
1757-6512 |
dc.identifier.doi.none.fl_str_mv |
10.1186/s13287-019-1223-z |
identifier_str_mv |
ALLAHDADI, Kyan James et al. IGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injury. Stem Cell Research & Therapy, v. 10, p. 1-14, 2019. 1757-6512 10.1186/s13287-019-1223-z |
url |
https://www.arca.fiocruz.br/handle/icict/34630 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
BMC |
publisher.none.fl_str_mv |
BMC |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
instname_str |
Fundação Oswaldo Cruz (FIOCRUZ) |
instacron_str |
FIOCRUZ |
institution |
FIOCRUZ |
reponame_str |
Repositório Institucional da FIOCRUZ (ARCA) |
collection |
Repositório Institucional da FIOCRUZ (ARCA) |
bitstream.url.fl_str_mv |
https://www.arca.fiocruz.br/bitstream/icict/34630/1/license.txt https://www.arca.fiocruz.br/bitstream/icict/34630/2/Allahdadi%2c%20K.J.%20IGF-%201%20overexpression%20improves...2019.pdf https://www.arca.fiocruz.br/bitstream/icict/34630/3/Allahdadi%2c%20K.J.%20IGF-%201%20overexpression%20improves...2019.pdf.txt |
bitstream.checksum.fl_str_mv |
5a560609d32a3863062d77ff32785d58 c2b7884b1d5910a32ab4890d450f15b8 183080281fe4c9a345e987c3f7360198 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ) |
repository.mail.fl_str_mv |
repositorio.arca@fiocruz.br |
_version_ |
1813009044977221632 |