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

Autor: Ricardo Ribeiro dos Santos, Carine Machado Azevedo, Bruno Solano Freitas de Souza, Daniela Nascimento Silva, Cristiane Flora Villarreal, Clarissa Valim, Roberta Alves Mota, Milena Botelho Pereira Soares, Thaís Alves de Santana, Renan Fernandes do Espírito Santo, Washington Luis Conrado dos Santos, Cláudio Pereira Figueira, Carolina Kymie Vasques Nonaka, Afrânio Ferreira Evangelista, Kyan James Allahdadi, Girlaine Café Santos
Rok vydání: 2018
Předmět:
0301 basic medicine
medicine.medical_treatment
Medicine (miscellaneous)
Bone Marrow Cells
Spinal cord injury
Mesenchymal Stem Cell Transplantation
Biochemistry
Genetics and Molecular Biology (miscellaneous)
Bone marrow-derived mesenchymal stem cells
Gene and cell therapy
lcsh:Biochemistry
03 medical and health sciences
Mice
0302 clinical medicine
Neural Stem Cells
Compact myelin
medicine
Animals
Humans
Regeneration
lcsh:QD415-436
Insulin-Like Growth Factor I
Myelin Sheath
Spinal Cord Injuries
lcsh:R5-920
business.industry
Growth factor
Research
Mesenchymal stem cell
Cell Differentiation
Mesenchymal Stem Cells
Cell Biology
Recovery of Function
medicine.disease
Neural stem cell
Transplantation
Disease Models
Animal
030104 developmental biology
Cytokine
030220 oncology & carcinogenesis
Cancer research
IGF-1
Molecular Medicine
Stem cell
business
lcsh:Medicine (General)
Zdroj: Stem Cell Research & Therapy
Stem Cell Research & Therapy, Vol 10, Iss 1, Pp 1-14 (2019)
ISSN: 1757-6512
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s13287-019-1223-z) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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