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BIBTEX RIS

IGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injury

2019; BioMed Central; Volume: 10; Issue: 1 Linguagem: Inglês

10.1186/s13287-019-1223-z

ISSN

1757-6512

Autores

Kyan James Allahdadi, Thaís Alves de Santana, Girlaine Café Santos, Carine Machado Azevedo, Roberta Alves Mota, Carolina Kymie Vasques Nonaka, Daniela Nascimento Silva, Clarissa X. R. Valim, Cláudio Pereira Figueira, Washington L. C. dos‐Santos, Renan Fernandes do Espírito Santo, Afrânio Ferreira Evangelista, Cristiane Flora Villarreal, Ricardo Ribeiro dos Santos, Bruno Solano de Freitas Souza, Milena Botelho Pereira Soares,

Tópico(s)

Spinal Dysraphism and Malformations

Resumo

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. 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. 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. 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.

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