Stem Cell Research & Therapy (May 2019)

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

  • Kyan James Allahdadi,
  • Thaís Alves de Santana,
  • Girlaine Café Santos,
  • Carine Machado Azevedo,
  • Roberta Alves Mota,
  • Carolina Kymie Nonaka,
  • Daniela Nascimento Silva,
  • Clarissa Xavier Resende Valim,
  • Cláudio Pereira Figueira,
  • Washington Luis Conrado dos Santos,
  • Renan Fernandes do Espirito Santo,
  • Afrânio Ferreira Evangelista,
  • Cristiane Flora Villarreal,
  • Ricardo Ribeiro dos Santos,
  • Bruno Solano Freitas de Souza,
  • Milena Botelho Pereira Soares

DOI
https://doi.org/10.1186/s13287-019-1223-z
Journal volume & issue
Vol. 10, no. 1
pp. 1 – 14

Abstract

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Abstract 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.

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