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Laminin-coated multifilament entubulation, combined with Schwann cells and glial cell line-derived neurotrophic factor, promotes unidirectional axonal regeneration in a rat model of thoracic spinal cord hemisection

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Neural Regeneration Research 2021年第1期16卷 186-191页

作者： Ling-Xiao Deng Nai-Kui Liu Ryan Ning Wen Shuang-Ni Yang Xuejun Wen Xiao-Ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteIndiana University School of MedicineIndianapolisINUSA Department of Neurological Surgery Indiana University School of MedicineIndianapolisINUSA Maggie L.Walker Governor’s School RichmondVAUSA Institute for Engineering and Medicine Department of Chemical and Life Science EngineeringVirginia Commonwealth UniversityRichmondVAUSA

Biomaterial bridging provides physical substrates to guide axonal growth across the *** achieve efficient directional guidance,combinatory strategies using permissive matrix,cells and trophic factors are *** the present study,we evaluated permissive effect of poly(acrylonitrile-co-vinyl chloride)guidance channels filled by different densities of laminin-precoated unidirectional polypropylene filaments combined with Schwann cells,and glial cell line-derived neurotrophic factor for axonal regeneration through a T10 hemisected spinal cord gap in adult *** found that channels with filaments significantly reduced the lesion cavity,astrocytic gliosis,and inflammatory responses at the graft-host *** laminin coated low density filament provided the most favorable directional guidance for axonal regeneration which was enhanced by co-grafting of Schwann cells and glial cell line-derived neurotrophic *** results demonstrate that the combinatorial strategy of filament-filled guiding scaffold,adhesive molecular laminin,Schwann cells,and glial cell line-derived neurotrophic factor,provides optimal topographical cues in stimulating directional axonal regeneration following spinal cord *** study was approved by Indiana University Institutional Animal Care and Use Committees(IACUC#:11011)on October 29,2015.

关键词： axonal regeneration extracellular molecule filament density hemisection laminin neurotrophic factor Schwann cell spinal cord injury thoracic transplantation

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Establishing A Precise Non-Human Primate Spinal Cord hemisection Injury Model: Devising A Replicable Platform to Study Tissue Engineering Based Therapy

Establishing A Precise Non-Human Primate Spinal Cord Hemisec...

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中国神经科学学会第十二届全国学术会议

作者： Xiang Zeng Yuanshan Zeng Jichao Ye Qingshuai Wei Junhua Rao Department of Histology and Embryolgoy Zhongshan School of Medicine Sun Yet-Sen University Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-Sen University) Ministry of Education Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of Medicine Sun Yat-sen University Department of spine surgery Sun Yat-Sen Memorial Hospital Sun Yat-Sen University Non-human Primate Research Center Guangdong Institute of Applied Biological Recourses

Objective Tissue engineering based therapy emerges as potent strategy in treating experimental spinal cord injury(SCI) in rodents. However, whether this treatment would be as safe and effect in clinical application still requires solid evidences in large animal, particularly, non-human primates(NHP), who embrace more interspecies similarities in biological, anatomical, pathological and pathophysiological features of human. So far there is a lack in standardized NHP SCI models optimal for evaluating implantable biomaterials or neuroengineering scaffolds. Buoyed by our success in establishing a clinical relevant NHP compression SCI model, here we introduce a novel NHP hemisection SCI model with precisely half cord removed by utilizing state-of-art intraoperative devices. Methods Intraoperative motor evoked potentials(MEP) was adopted in monitoring the completeness of the hemi resection(4 mm longitudinal) as well as the integrity of the controlateral motor tracts of the spinal cord in anesthetized Macaca fascicularis. An adjuvant laser speckle blood flowmetry allowed a real-time quantification of the underlying unexposed tissue. As a proof of model applicability, a "D" shape three dimensional gelatin sponge scaffold(3 D GS) was applied in the hemisection site after modeling. The animals were evaluated weekly for their hindlimb motor function by Locomotor observational rating score(LORS, a total 36 score scale).The Kinematics of hind limbs was assessed by Primate Scan behavioral recording system. MRI and diffusion tensor imaging(DTI) were carried out 2 weeks post surgery and thereafter monthly to confirm the hemisection and the following tissue regeneration progress. All monkeys were terminated 2 month after SCI and spinal cord tissue was processed for histopathological evaluation. Results The combination of intraoperative MEP and laser speckle blood flowmetry guaranteed a precise hemisection of the spinal cord. Post operative MRI and DTI confirmed the loss of half cord

关键词： Spinal cord injury Non human primate hemisection Tissue engineering Gelatin sponge scaffold

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A comparative analysis of differentially expressed genes in rostral and caudal regions after spinal cord injury in rats

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Neural Regeneration Research 2022年第10期17卷 2267-2271页

作者： Xue-Min Cao Sheng-Long Li Yu-Qi Cao Ye-Hua Lv Ya-Xian Wang Bin Yu Chun Yao Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsCo-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina

The initial mechanical damage of a spinal cord injury(SCI)triggers a progressive secondary injury cascade,which is a complicated process integrating multiple systems and *** is crucial to explore the molecular and biological process alterations that occur after SCI for therapy *** differences between the rostral and caudal regions around an SCI lesion have received little ***,we analyzed the differentially expressed genes between rostral and caudal sites after injury to determine the biological processes in these two segments after *** identified a set of differentially expressed genes,including Col3a1,Col1a1,Dcn,Fn1,Kcnk3,and Nrg1,between rostral and caudal regions at different time points following *** enrichment analysis indicated that these genes were involved in response to mechanical stimulus,blood vessel development,and brain *** then chose Col3a1,Col1a1,Dcn,Fn1,Kcnk3,and Nrg1 for quantitative real-time PCR and Fn1 for immunostaining *** results indicate alterations in different biological events enriched in the rostral and caudal lesion areas,providing new insights into the pathology of SCI.

关键词： biological process caudal differentially expressed genes Gene Ontology hemisection immunostaining Rattus norvegicus RNA-sequencing rostral spinal cord injury

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