The SDF-1/CXCR4 axis promotes recovery after spinal cord injury by mediating bone marrow-derived from mesenchymal stem cells.

Guo-Dong Wang,Ya-Dong Zhang,Feng Xue,Yong-Le Zhang,Xiao Wang,Yi-Xun Liu

doi:10.18632/oncotarget.14619

Guo-Dong Wang, Ya-Dong Zhang + Show 4 more

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https://doi.org/10.18632/oncotarget.14619

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Abstract

This study aims to explore the role of the SDF-1/CXCR4 axis in mediating BMSCs and SCI recovery. BMSCs were collected and SCI rat models were established. Wistar rats were assigned into the blank control, sham, SCI, SCI + BMSCs, SCI + BMSCs + SDF-1, SCI + BMSCs + AMD3100 (an inhibitor of SDF-1/CXCR4 axis) and SCI + BMSCs + SDF-1 + AMD3100 groups. Hind limb motor function was measured 7, 14, 21 and 28 days after operation. qRT-PCR, western blotting and ELISA was performed to determine the expressions of SDF-1, CXCR4, NGF, BDNF, GFAP and GAP-43, TNF-α, IL-1β, L-6 and IFN-γ. Hind limb motor function scores 7 days after the operation were reduced in the SCI rats of the blank control and sham groups. Hind limb function was found to be better in the SCI + BMSCs and SCI + BMSCs + SDF-1 groups than in the SCI, SCI + BMSCs + AMD3100 and SCI + BMSCs + SDF-1 + AMD3100 groups 14, 21 and 28 days after operation. Furthermore, the SCI group had lower SDF-1, CXCR4, NGF, BDNF and GAP-43 expressions but higher GFAP, TNF-α, IL-1β, IL-6 and IFN-γ than the blank control and sham groups 28 days after operation. While, the SCI + BMSCs, SCI + BMSCs + SDF-1 and SCI + BMSCs + SDF-1 + AMD3100 groups displayed opposite trends to the SCI and SCI + BMSCs + AMD3100 groups. In conclusion, SDF-1/CXCR4 axis promotes recovery after SCI by mediating BMSCs.

Highlights

Spinal cord injury (SCI) is a highly disabling disease which causes disorder loss of sensory and motion function and results in the functional disorders of many other systems such as the respiratory, circulatory, urinary and digestive systems [1, 2]
This study aims to explore the role of the SDF-1/chemotaxis cytokine receptor-4 (CXCR4) axis in mediating bone marrow mesenchymal stem cells (BMSCs) and SCI recovery
When compared with the blank control and sham groups, the expressions of SDF-1, CXCR4, NGF, BDNF and GAP-43 decreased while GFAP expression increased in the SCI, SCI + BMSCs, SCI + BMSCs + AMD3100 and SCI + BMSCs + SDF-1 + AMD3100 groups

Summary

Introduction

Spinal cord injury (SCI) is a highly disabling disease which causes disorder loss of sensory and motion function and results in the functional disorders of many other systems such as the respiratory, circulatory, urinary and digestive systems [1, 2]. It is estimated that the morbidity of SCI over the world is about 236 to 1,009 per million [3]. Young adults and male patients are more prone to SCI [1]. The pathology of SCI is mainly broken into primary and secondary SCI. Secondary SCI pathology aggravates the disease and edema, causes degeneration and the necrosis of damaged neurons [4, 5]. SCI treatment is a research hotspot due to its high disability rate and heavy social burden

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