Demyelination is a nervous system disease in which the myelin sheaths of neurons are damaged due to inflammatory reactions, inherited abnormalities or trauma. This damage impairs the conduction of signals in the affected nerves, which in turn causes deficiencies in sensation, movement and cognition. Oligodendrocyte precursor cells (OPCs) are able to induce remyelination. However, the remyelination is suboptimal due to the limited migration of OPCs. In the present study, neonatal OPCs were isolated from rats for the investigation of the role of C-X-C motif chemokine ligand 12 (CXCL12), an important chemokine, in mediating the migration ability of OPCs. The present results demonstrated that CXCL12 stimulation markedly promoted the migration of OPCs and activated the dual specificity mitogen-activated protein kinase kinase 1 (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/RAC-α serine/threonine-protein kinase (AKT) pathways. Knockdown of C-X-C motif chemokine receptor 4 (CXCR4; a receptor of CXCL12) reversed the CXCL12-induced migration of OPCs and blocked the MEK/ERK and PI3K/AKT pathways. In addition, specific inhibitors of the MEK/ERK and PI3K/AKT pathways significantly reduced the migration of OPCs. Based on these findings, it was concluded that CXCL12 may induce the migration of OPCs through the CXCR4-activated MEK/ERK and PI3K/AKT pathways. The results of the present study support the manipulation of CXCL12-mediated OPC migration to improve remyelination.
In recent years, acellular spinal cord scaffolds have been extensively studied in tissue engineering. Notably, acellular spinal cord scaffolds may be used to treat spinal cord injury; however, the method of preparation can result in low efficiency and may affect the biological properties of cells. This study aimed to use EDC crosslinking, combined with chemical extraction for tissue decellularization, in order to improve the efficiency of acellular scaffolds. To make the improved stent available for the clinical treatment of spinal cord injury, it is necessary to study its immunogenicity. Therefore, this study also focused on the adherence of rat bone marrow mesenchymal stem cells to scaffolds, and their differentiation into neuron-like cells in the presence of suitable trophic factors. The results revealed that EDC crosslinking combined with chemical extraction methods may significantly improve the efficiency of acellular scaffolds, and may also confer better biological characteristics, including improved immunogenicity. Notably, it was able to promote adhesion of rat bone marrow mesenchymal stem cells and their differentiation into neuron-like cells. These results suggested that the improved preparation method may be promising for the construction of multifunctional acellular scaffolds for the treatment of spinal cord injury.
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