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

• Published in: Stem Cell Research & Therapy 2019, Vol.10 (1)
• Main Authors: Allahdadi, Kyan James, de Santana, Thaís Alves, Santos, Girlaine Café, Azevedo, Carine Machado, Mota, Roberta Alves, Nonaka, Carolina Kymie, Silva, Daniela Nascimento, Valim, Clarissa Xavier Resende, Figueira, Cláudio Pereira, dos Santos, Washington Luis Conrado, do Espirito Santo, Renan Fernandes, Evangelista, Afrânio Ferreira, Villarreal, Cristiane Flora, dos Santos, Ricardo Ribeiro, de Souza, Bruno Solano Freitas, Soares, Milena Botelho Pereira
• Format: Report
• Language: English
• Subjects: Antioxidants (Nutrients); Care and treatment; Cytokines; Gene expression; Genes; Homeostasis; House mouse; Insulin; Insulin-like growth factor I; Oxidative stress; Spinal cord injuries; Stem cell transplantation; Stem cells; Surgery
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-019-1223-z

Background 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. Keywords: Spinal cord injury, Bone marrow-derived mesenchymal stem cells, IGF-1, Gene and cell therapy