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Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia george smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA Department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals Pediatric Research Center Temple University School of MedicinePhiladelphiaPAUSA Department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

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Acetylation as a mechanism that regulates axonal regeneration

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Neural Regeneration Research 2015年第7期10卷 1034-1036页

作者： Shen Lin george M.smith Shriners Hospitals for Pediatric Research Center Department of Neuroscience Temple University

The capacity for adult axons to regenerate after injury is diminished compared with developing *** the case of central nervous system（CNS）axons,injury causes a total failure to *** failure is due to both the intrins... 详细信息

关键词： gene HDAC Acetylation as a mechanism that regulates axonal regeneration

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Neurotrophin treatment to promote regeneration after traumatic CNS injury

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Frontiers in Biology 2013年第5期8卷 486-495页

作者： Lakshmi KELAMANGALATH george M. smith Center for Neural Repair and Rehabilitation Department of Neuroscience & Shriners Hospitals for Pediatric Research Temple UniversitySchool of Medieine Philadelphia PA 19140-4106 USA

Neurotrophins are a family of growth factors that have been found to be central for the development and functional maintenance of the nervous system, participating in neurogenesis, neuronal survival, axonal growth, synaptogenesis and activity-dependent forms of synaptic plasticity. Trauma in the adult nervous system can disrupt the functional circuitry of neurons and result in severe functional deficits. The limitation of intrinsic growth capacity of adult nervous system and the presence of an inhospitable environment are the major hurdles for axonal regeneration of lesioned adult neurons. Neurotrophic factors have been shown to be excellent candidates in mediating neuronal repair and establishing functional circuitry via activating several growth signaling mechanisms including neuron-intrinsic regenerative programs. Here, we will review the effects of various neurotrophins in mediating recovery after injury to the adult spinal cord.

关键词： axonal guidance neurotrophin regeneration functional recovery sprouting

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Reactive astrocyte scar and axon regeneration:suppressor or facilitator?

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Neural Regeneration Research 2016年第7期11卷 1050-1051页

作者： Yosuke Ohtake george M.smith Shuxin Li Shriners Hospitals Pediatric Research Center Department of Anatomy and Cell BiologyDepartment of NeuroscienceLewis Katz School of Medicine at Temple University

Several major factors are known to contribute to CNS axon regenerative failure after injury, including reduced intrinsic growth capacity of developed neurons and extrinsic factors mediating axon outgrowth. For the latter, a non-permissive environment around the lesion and the lack of sufficient neurotrophic support within the adult CNS play important roles （Silver et al., 2015）. In addition to generation of various inhibitory substrates by oligodendrocytes, fibrotic tissues, inflammatory cells and other cell types, reactive astrocytes surrounding lesions are thought to highly suppress regeneration of injured CNS axons （Silver and Miller, 2004; Ohtake and Li, 2014）. A great number of studies suggest that reactive astrocytic scars form one of the major barriers preventing axon regeneration after CNS iniuries, including spinal cord injury （SCI）. However, reactive astrocytes were reported to provide a beneficial role by reducing infiltrating immunoreactive cells into adjacent domains, protecting bordering neural tissue from damage and generating numerous supportive extracellular matrix （ECM） components to promote cell survival and growth （Bush et al., 1999）. Previ- ous data showed that ablation of reactive astrocytes increased inflammation and secondary tissue damage, prevented blood- brain barrier formation and increased local neurite growth. Interestingly, a recent study by Anderson et al （2016） provides evidence that reactive astrocytes around the lesioned spinal cord support axon regeneration after SCI, rather than block regrowth （Anderson et al., 2016）.

关键词： astrocyte regeneration suppressor neurotrophic extrinsic latter intrinsic glial injured sensory

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Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

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Neural Regeneration Research 2025年第4期20卷 1192-1206页

作者： Tyler A.smith Liwen Zhou Cameron L.Ghergherehchi Michelle Mikesh Cathy Z.Yang Haley O.Tucker JuliAnne Allgood Jared S.Bushman george D.Bittner Department of Molecular Biosciences University of Texas at AustinAustinTXUSA Department of Neuroscience University of Texas at AustinAustinTXUSA Division of Pharmaceutical Sciences University of WyomingLaramieWYUSA

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal ***,such peripheral nerve allografts undergo immunological rejection by the host immune *** contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian *** relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this *** hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral *** examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal ***-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host *** to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days *** morphological signs of rejection,such as col

关键词： allograft rejection axotomy macrophage myelin nerve repair polyethylene glycol(PEG) sciatic nerve T cell transplantation Wallerian degeneration

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用于慢性十二指肠溃疡的迷走神经干切断术和胃肠吻合术的手术年龄及效果

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右江医学 1984年第1期 40-42页

作者： george smith 李瑞锦

在英国以外的地方,迷走神经干切断术和胃空肠吻合术作为慢性十二指肠溃疡治疗常规的选择方法曾得到少数人的支持。对照试验结果表明:胃空肠吻合术和幽门成形术并迷走神经干切断术的效果略有不同。在北美洲,迷走神经干切断术并胃切除术... 详细信息

在英国以外的地方,迷走神经干切断术和胃空肠吻合术作为慢性十二指肠溃疡治疗常规的选择方法曾得到少数人的支持。对照试验结果表明:胃空肠吻合术和幽门成形术并迷走神经干切断术的效果略有不同。在北美洲,迷走神经干切断术并胃切除术被广泛采用。新近,近端胃迷走神经切断术已成为流行方法。对一组施行迷走神经干切断术和后侧胃空肠吻合术的305名病例有关复发和副作用方面进行重查,显示这种手术令人满意,特别是手术年龄在40岁以上的那些病人病人和方法有X线和内窥镜根据,经内科试验治疗但仍有严重症状包括延误工作和睡眠障碍的305名连续的慢性十二指肠溃疡病人接受手

关键词：迷走神经干切断术胃空肠吻合术幽门成形术手术胃肠吻合术十二指肠溃疡消化性溃疡女病人

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GDNF-Enhanced Axonal Regeneration and Myelination Following Spinal Cord Injury is Mediated by Primary Effects on Neurons

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神经损伤与功能重建 2009年第4期4卷 268-281页

作者： LIQUN ZHANG ZHENGWEN MA george M. smith XUEJUN WEN YELENA PRESSMAN PATRICK M. WOOD AND XIAO-MING XU Kentucky Spinal Cord Injury Research Center Departments of Neurological Surgery and Ana-tomical Sciences and NeurobiologyUniversity of Louisville School of Medicine Louisville Kentueky Department of Orthopedics The First Affiliated Hospital of Fujian Medical University Fuzhou Fujian People＇s Republic of China Spinal Cord and Brain Injury Research Center Department of Physiology University of Kentucky Chandler Medical Center Lexington Kentucky Clemson-MUSC Joint Bioengi- neering Program Charleston South Carolina The Miami Project to Cure Paralysis Departments of Neurological Surgery University of Miami School of Medicine MiamiFlorida Spinal Cord and Brain Injury Research Group Stark Neurosciences Research Institute and Department of Neurological Surgery Indiana University School of Medicine Indianapolis Indiana

我们先前研究表明胶质细胞源性神经营养因子(GDNF)联合施万细胞移植能促进脊髓损伤后轴突再生和髓鞘形成。然而,GDNF介导这一过程的细胞靶点尚不清楚。在此,我们报道了GDNF可增加在体再生轴突的数目和直径,并促进体外背根神经节神经元... 详细信息

我们先前研究表明胶质细胞源性神经营养因子(GDNF)联合施万细胞移植能促进脊髓损伤后轴突再生和髓鞘形成。然而,GDNF介导这一过程的细胞靶点尚不清楚。在此,我们报道了GDNF可增加在体再生轴突的数目和直径,并促进体外背根神经节神经元的轴突向外生长,提示GDNF对神经元有直接作用。在施万细胞-背根神经节神经元共培养下,GDNF显著增加施万细胞生成的髓鞘数目;GDNF处理对孤立培养的施万细胞增殖无作用,但可促进已与神经轴突有突触联系的施万细胞增殖;GDNF可增加孤立施万细胞中分子量为140kDa的神经细胞黏附分子(NCAM)的表达,但对黏附分子L1表达或神经营养因子NGF、NT3及BDNF分泌没有影响。总之,这些结果支持假设:GDNF提高轴突再生和施万细胞髓鞘形成主要是通过GDNF对神经元的直接作用介导的,并且提示GDNF联合施万细胞移植可能是促进脊髓损伤后轴突再生和髓鞘形成的有效策略之一。

关键词： GDNF 轴突髓鞘形成再生施万细胞脊髓损伤

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如何选择无流道系统

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模具工业 1991年第10期17卷 61-63页

作者： george smith 李和平

本文说的是:市场上出售的无流道系统,并非对任何材料的成形都适用,对无流道系统的选择和应用的正确与否,则往往就决定了模具设计的成败。本文的目的就在于帮助模具设计者如何正确地选择无流道系统。

关键词：模具无流道系统塑料集流腔

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Identification of a Novel miRNA in Melanocytes of Alpaca(Lama Pacos)

Identification of a Novel miRNA in Melanocytes of Alpaca(Lam...

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中国畜牧兽医学会动物解剖及组织胚胎学分会第十八次学术研讨会

作者： Ruiwen Fan Shanshan Yang Zhanquan Shi Kaiyuan Ji Xiaoyun Jia Jianbo Yao george W smith Changsheng Dong College of Animal Science and Technology Shanxi Agricultural University Laboratory of Animal Biotechnology and Genomics Division of Animal and Nutritional SciencesWest Virginia University Laboratory of Mammalian Reproductive Biology and Genomics Departments of Animal Science and PhysiologyMichigan State University

From the previous deep sequencing of alpaca skins,one of novel miRNAs expressed differently in white and black alpaca skin(named alp-miR066).According to the target gene prediction,one of the target genes is soluble guanylate cyclase(sGC).To get the function of alp-miR-066 in alpaca skin,it was over expressed in alpaca melanocytes in *** expression of miRNA-066 was tested by real-time PCR and the results showed it expressed *** the pathway of cAMP in melanocytes,cGMP was increased by ELASA assay,while cAMP was *** expression of sGC,TYR,TYRP1,TYRP2 and MITF protein were tested by western blotting,and the results showed that sGC was increased and TYR,TYRP1 and MITF protein were ***,the number of melanogenic melanocytes was less and the amount of melanins production was 0.7 fold in alp-miR066 transfection group,compared to Negative control(NC) transfection *** those results suggested that alp-miR-066 might regulate melanogenesis on the pathway of cAMP in alpaca melanocytes by targeting sGC.

关键词： alp-miR066 melanocytes cAMP melanin sGC

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Identification of a novel miRNA important for melanogenesis in alpaca(Lama Pacos)

Identification of a novel miRNA important for melanogenesis ...

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提升骆驼产业科技含量，打造骆驼行业知名品牌——第二届（2013）中国骆驼大会

作者： Ruiwen Fan Shanshan Yang Zhanquan Shi Kaiyuan Ji Xiaoyun Jia Jianbo Yao george W smith Changsheng Dong

The mechanism of coat color formation is complex,microRNAs play important roles in the control of melanogenesis and coat color in *** the previous deep sequencing of alpaca skins,one of novel miRNAs expressed differently in white and black alpaca skin(named alp-miR066).According to the target gene prediction,one of the target genes is soluble guanylate cyclase(sGC).To get the function of alp-miR-066 in alpaca skin,it was over expressed in alpaca melanocytes in *** expression of miRNA-066 was tested by real-time PCR and the results showed it expressed *** the pathway of cAMP in melanocytes,cGMP was increased by ELASA assay,while cAMP was decreased. The expression of sGC,TYR,TYRP1,TYRP2 and MITF protein were tested by western blotting,and the results showed that sGC was increased and TYR,TYRP1 and MITF protein were ***,the number of melanogenic melanocytes was less and the amount of melanins production was 0.7 fold in alp-miR066 transfection group,compared to negative control(NC) transfection *** those results suggested that alp-miR-066 might regulate melanogenesis on the pathway of cAMP in alpaca melanocytes by targeting sGC.

关键词： alp-miR066 melanocytes cAMP melanin sGC

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