Transplantation of Nogo-66 receptor gene-silenced cells in a poly(D,L-lactic-co-glycolic acid) scaffold for the treatment of spinal cord injury |
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Authors: | Dong Wang Yuhong Fan Jianjun Zhang |
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Institution: | Dong Wang (Department of Neurosurgery, Tianjin Fourth Central Hospital, Tianjin 300140, China);Yuhong Fan (Department of Stomatology, First Clinical College, Hebei North University, Zhangjiakou 075000, Hebei Province, China);Jianjun Zhang (Department of Neurosurgery, Tianjin Fourth Central Hospital, Tianjin 300140, China); |
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Abstract: | Inhibition of neurite growth, which is in large part mediated by the Nogo-66 receptor, affects neural regeneration following bone marrow mesenchymal stem cell transplantation. The tissue engineering scaffold poly(D,L-lactide-co-glycolic acid) has good histocompatibility and can promote the growth of regenerating nerve fibers. The present study used small interfering RNA to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells and Schwann cells, which were subsequently transplanted with poly(D,L-lactide-co-glycolic acid) into the spinal cord lesion regions in rats. Simultaneously, rats treated with scaffold only were taken as the control group. Hematoxylin-eosin staining and immunohistochemistry revealed that at 4 weeks after transplantation, rats had good motor function of the hind limb after treatment with Nogo-66 receptor gene-silenced cells plus the poly(D,L-lactide-co-glycolic acid) scaffold compared with rats treated with scaffold only, and the number of bone marrow mesenchymal stem cells and neuron-like cells was also increased. At 8 weeks after transplantation, horseradish peroxidase tracing and transmission electron microscopy showed a large number of unmyelinated and myelinated nerve fibers, as well as intact regenerating axonal myelin sheath following spinal cord hemisection injury. These experimental findings indicate that transplantation of Nogo-66 receptor gene-silenced bone marrow mesenchymal stem cells and Schwann cells plus a poly(D,L-lactide-co-glycolic acid) scaffold can significantly enhance axonal regeneration of spinal cord neurons and improve motor function of the extremities in rats following spinal cord injury. |
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Keywords: | neural regeneration spinal cord injury bone marrow mesenchymal stem cells Schwann cells poly(D L-lactide-co-glycolic acid) Nogo-66 receptor gene rats gene silencing grants-supported paper photographs-containing paper neuroregeneration |
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