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IGF-1 OVEREXPRESSION IMPROVES MESENCHYMAL STEM CELL SURVIVAL AND PROMOTES NEUROLOGICAL RECOVERY AFTER SPINAL CORD INJURY
Células-tronco mesenquimais derivadas da medula óssea
IGF-1
Terapia gênica e celular
Author
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Abstract
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 in Portuguese
Lesão medularCélulas-tronco mesenquimais derivadas da medula óssea
IGF-1
Terapia gênica e celular
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