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IGF-1 OVEREXPRESSION IMPROVES MESENCHYMAL STEM CELL SURVIVAL AND PROMOTES NEUROLOGICAL RECOVERY AFTER SPINAL CORD INJURY
Allahdadi, Kyan James et al. | Fecha del documento: 2019
Autor
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
Afiliación
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, 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.
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.
Resumen en ingles
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.
Palabras clave en portugues
Lesão medular
Células-tronco mesenquimais derivadas da medula óssea
IGF-1
Terapia gênica e celular
 
Palabras clave en ingles
Spinal cord injury
Bone marrow-derived mesenchymal stem cells
IGF-1
Gene and cell therapy
 
Editor
BMC
Referencia
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.
DOI
10.1186/s13287-019-1223-z
ISSN
1757-6512