Influence of olfactory ensheathing cell transplantation on body temperature of patients with old spinal cord injury

BACKGROUND:Olfactory ensheathing cell transplantation may transiendy raise body temperature in some patients with old spinal cord injury.OBJECTIVE:To analyze the influence of olfactory ensheathing cell transplantation on body temperature changes and neurological functional recovery in patients with old spinal cord injury.DESIGN,TIME AND SETTING:A non-randomized self-controlled study,which was performed in the wards of the Department of Surgery,Taian Disabled Soldier's Hospital of Shandong Province.between June 2004 and July 2007.PARTICIPANTS:119 inpatients with old spinal cord injury were selectcd for this study,including 110 males and 9 females,aged 5-58 years.METHODS:The olfactory bulb of an aborted fetus was digested into a single-cell suspension of olfactory ensheathing cells.which were then cultured and purified for 7-10 days,and once again made into a single-cell suspension.The elfactory ensheathing cell suspension was then transplanted in the iuncture of the normal spinal cord and the abnormal spinal cord under surgical microscopy,with 1 ×10°cells per target point,with 2-5 target points in total.According to changes in postoperative temperature,119 patients were divided into three groups:body temperature(T)≤38.0℃(n=40),38.0℃39.0℃(n=12).In particular,T>38℃(n=79)patients were divided into two subgroups according to duration of fever:≤3 days(n=61)and≥4days(n=18).MAIN OUTCOME MEASURES:Neurological function was evaluated by the American Spinal Cord Injury(ASIA)scale set by American Spinal Cord Injury Academy in 2000 one day prior to transplantation and one or two months after transplantation.RESUITS:119 patients were included in the final analysis,without any loss.Following olfactory ensheathing cell transplantation,body temperatures changed as follows:T≤38.0℃(n=40,33.6%),38.0℃39.0℃(n=12,10.1%).Moreover,among 79 patients(T>38℃),the febrile time of 61 cases(77%)was≤3 days,and that of 18 cases(23%)≥4 days.ASIA scores increased after olfactory ensheathing cell transplantation (P<0.05 0.01).CONCLUSION:Moderate febricity frequently occurred jn patients tbat received olfactory ensheathing cell transplantation,and febrile time lasted for more than 3 days.Additionally,olfactory ensheathing cell transplantation can remarkably improve neurological functional recovery.     

Meta analysis of olfactory ensheathing cell transplantation promoting functional recovery of motor nerves in rats with complete spinal cord transection

OBJECTIVE:To evaluate the effects of olfactory ensheathing cell transplantation on functional recovery of rats with complete spinal cord transection.DATA SOURCES: A computer-based online search of Medline(1989–2013),Embase(1989–2013),Cochrane library(1989–2013),Chinese Biomedical Literature Database(1989–2013),China National Knowledge Infrastructure(1989–2013),VIP(1989–2013),Wanfang databases(1989–2013) and Chinese Clinical Trial Register was conducted to collect randomized controlled trial data regarding olfactory ensheathing cell transplantation for the treatment of complete spinal cord transection in rats.SELECTION CRITERIA: Randomized controlled trials investigating olfactory ensheathing cell transplantation and other transplantation methods for promoting neurological functional recovery of rats with complete spinal cord transection were included in the analysis.Meta analysis was conducted using Rev Man 4.2.2 software.MAIN OUTCOME MEASURES: Basso,Beattie and Bresnahan scores of rats with complete spinal cord transection were evaluated in this study.RESULTS: Six randomized controlled trials with high quality methodology were included.Meta analysis showed that Basso,Beattie and Bresnahan scores were significantly higher in the olfactory ensheathing cell transplantation group compared with the control group(WMD = 3.16,95% CI(1.68,4.65); P 0.00001).CONCLUSION: Experimental studies have shown that olfactory ensheathing cell transplantation can promote the functional recovery of motor nerves in rats with complete spinal cord transection.     

Transplantation of olfactory ensheathing cells for promoting regeneration following spinal cord injury

OBJECTIVE： To investigate the status of olfactory ensheathing cells （OECs） transplantation in facilitating the regeneration of spinal cord injury. DATA SOURCES： Articles about OECs transplantation in treating spinal cord injury were searched in Pubmed database published in English from January 1981 to December 2005 by using the keywords of ＂olfactory ensheathing cells, transplantation, spinal cord injury＂. STUDY SELECTION： The data were checked primarily, literatures related to OECs transplantation and the regeneration of spinal cord injury were selected, whereas the repetitive studies and reviews were excluded. DATA EXTRACTION： Totally 43 articles about OECs transplantation and the regeneration and repair of spinal cord injury were collected, and the repetitive ones were excluded. DATA SYNTHESIS： There were 35 articles accorded with the criteria. OECs are the olfactory ensheathing glias isolated from olfactory bulb and olfactory nerve tissue. OECs have the characters of both Schwann cells in central nervous system and peripheral astrocytes. The transplanted OECs can migrate in the damaged spinal cord of host, can induce and support the regeneration, growth and extension of damaged neuritis. Besides, transgenic technique can enable it to carry some exogenous genes that promote neuronal regeneration, and express some molecules that can facilitate neural regeneration, so as to ameliorate the internal environment of nerve injury, induce the regeneration of damaged spinal cord neurons, which can stimulate the regeneration potential of the damaged spinal cord to reach the purpose of spinal cord regeneration and functional recovery. CONCLUSION： OECs are the glial cells with the energy for growth at mature phase, they can myelinize axons, secrete various biological nutrition factors, and then protect and support neurons, also facilitate neural regeneration. OECs have been successfully isolated from nasal olfactory mucosa and olfactory nerve. Therefore, autologous transplantation of OECs and objective genes modified OECs carrying various neurotrophic factors may become an effective method to treat spinal cord injury in the future.     

移植分泌神经营养素3的人胚神经干细胞在脊髓损伤大鼠体内存活及对运动功能的影响

BACKGROUND： Many methods have been attempted to repair nerves following spinal cord injury, including peripheral nerve transplantation, Schwann cell transplantation, olfactory ensheathing cell transplantation, and embryonic neural tissue transplantation. However, there is a need for improved outcomes.
OBJECTIVE： To investigate the repair feasibility for rat spinal cord injury using human neural stem cells （hNSCs） genetically modified by lentivirus to express neurotrophin-3.
DESIGN, TIME AND SETTING： In vitro cell biological experiment and in vivo randomized, controlled genetic engineering experiment were performed at the Third Military Medical University of Chinese PLA and First People＇s Hospital of Yibin, China from March 2006 to December 2007.
MATERIALS： A total of 64 adult, female, Wistar rats were used for the in vivo study. Of them, 48 rats were used to establish models of spinal cord hemisection, and were subsequently equally and randomly assigned to model, genetically modified hNSC, and normal hNSC groups. The remaining 16 rats served as normal controls.
METHODS： hNSCs were in vitro genetically modified by lentivirus to secrete both green fluorescence protein and neurotrophin-3. Neurotrophin-3 expression was measured by Western blot. Genetically modified hNSC or normal hNSC suspension （5 × 10^5） was injected into the rat spinal cord following T10 spinal cord hemisection. A total of 5μL Dulbecco＇s-modified Eagle＇s medium was infused into the rat spinal cord in the model grop. Transgene expression and survival of transplanted hNSCs were determined by immunohistochemistry. Motor function was evaluated using the Basso, Beattie, and Bresnahan （BBB） scale.
MAIN OUTCOME MEASURES： The following parameters were measured： expression of neurotrophin-3 produced by genetically modified hNSCs, transgene expression and survival of hNSCs in rats, motor function in rats.
RESULTS： hNSCs were successfully genetically modified by lentivirus to stably express neurotrophin-3. The transplanted hNSCs primarily gathered at, or around, the injection site two weeks following transplantation, and gradually migrated towards the surrounding tissue. Transplanted hNSCs were observed 7.0-8.0 mm away from the injection site. In addition, hNSCs were observed 10 weeks after transplantation. At week 4, BBB locomotor scores were significantly greater in the genetically modified hNSC and normal hNSC groups, compared with the model group （P 〈 0.05）, and scores were significantly greater in the genetically modified hNSC group compared with the normal hNSC group （P 〈 0.05）.
CONCLUSION： hNSCs were genetically modified with lentivirus to stably secrete neurotrophin-3. hNSCs improved motor function recovery in rats following spinal cord injury.     

Transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury A Web of Science-based literature analysis

OBJECTIVE: To identify global research trends in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. DATA RETRIEVAL: We performed a bibliometric analysis of studies on transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury published from 2002 to 2011 and retrieved from the Web of Science, using the key words spinal cord injury along with either neural stem cell, Schwann cell or olfactory ensheathing cell. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on neural stem cells, Schwann cells or olfactory ensheathing cells for spinal cord injury indexed in the Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial materials and news items; and (c) published between 2002 and 2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) corrected papers. MAIN OUTCOME MEASURES: (1) Annual publication output, distribution by journal, distribution by institution and top-cited articles on neural stem cells; (2) annual publication output, distribution by journal, distribution by institution and top-cited articles on Schwann cells; (3) annual publication output, distribution by journal, distribution by institution and top-cited articles on olfactory ensheathing cells. RESULTS: This analysis, based on articles indexed in the Web of Science, identified several research trends among studies published over the past 10 years in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. The number of publications increased over the 10-year period examined. Most papers appeared in journals with a focus on neurology, such as Journal of Neurotrauma, Experimental Neurology and Glia. Research institutes publishing on the use of neural stem cells to repair spinal cord injury were mostly in the USA and Canada. Those publishing on the use of Schwann cells were mostly in the USA and Canada as well. Those publishing on the use of olfactory ensheathing cells were mostly in the UK, the USA and Canada. CONCLUSION: On the basis of the large number of studies around the world, cell transplantation has proven to be the most promising therapeutic approach for spinal cord injury.     

微囊化兔坐骨神经组织细胞移植对大鼠损伤脊髓核因子κB表达的影响

BACKGROUND： It has been reported that nuclear factor-kappa B （NF- κB）, activated after spinal cord injury in rats, plays a key role in inflammatory responses in the central nervous system. OBJECTIVE： To investigate the effects of transplantation of microencapsulated rabbit sciatic nerve on NF- κB expression and motor function after spinal cord injury in rats, and to compare the results with the transplantation of rabbit sciatic nerve alone. DESIGN, TIME AND SETTING： This completely randomized, controlled study was performed at the Department of Neurobiology, Medical College of Nanchang University between December 2007 and July 2008. MATERIALS： A rabbit anti-NF- κB P65 monoclonal antibody was made by the Santa Cruz Company, USA and a streptavidin peroxidase immunohistochemical kit was provided by the Sequoia Company, China. METHODS： Eight rabbits were used to prepare a sciatic nerve cell suspension that was divided into two parts： one stored for transplantation, and the other mixed with a 1.5% sodium alginate solution. One hundred and twenty adult Sprague Dawley rats weighing 220-250 g were randomly divided into four groups： the microencapsulated cell group （n = 36）, the non-encapsulated cell group （n = 36）, the saline group （n = 36） and the sham operation group （n = 12）. The first three groups underwent a right hemisection injury of the spinal cord at the T10 level, into which was transplanted a gelatin sponge soaked with 10 μL of a microencapsulated nerve tissue/cell suspension （microencapsulated cell group）, a tissue/cell suspension （non-encapsulated cell group） or physiological saline （saline group）. In the sham operation group the vertebrae were exposed, but the spinal cord was not injured, and no implantation was given. MAIN OUTCOME MEASURES： Pathological changes were detected using hematoxylin-eosin staining; NF- κB expression was quantified using immunohistochemical staining; motor function was assessed using the Basso, Beattie and Bresnahan （BBB） scale. RESULTS： Spinal cord injuries, such as neuronal death and inflammatory cell infiltration, were found in the microencapsulated cell group, the non-encapsulated cell group and the saline group. However, the damage in the microencapsulated cell group was milder than in the non-encapsulated cell or saline groups. NF- κB expression in the microencapsulated cell group, the non-encapsulated cell group and the saline group was increased after spinal cord injury; it reached a peak after 24 hours, gradually decreased after 3 days, and was close to normal levels after 7 days. NF- κB expression in the microencapsulated cell group was significantly lower than in the saline group and the non-encapsulated cell group （P 〈 0.05）. With time, the motor function of the animals in each group improved to a certain extent, but did not reach normal levels. There were no significant differences in BBB scores between the different groups on post-operative day 3; however, the BBB scores for the microencapsulated cell group and the non-encapsulated cell group were significantly higher than the saline group on post-operative day 7 （P 〈 0.05）. In addition, the motor function recovered better in the microencapsulated cell group than in the non-encapsulated cell group （P 〈 0.05）. CONCLUSION： The transplantation of microencapsulated rabbit sciatic nerve can inhibit NF- κB expression and inflammatory reactions and promote recovery of motor function after spinal cord injury in rats. The effects of microencapsulated cell transplantation are superior to those of transplantation of cells alone.     

自身免疫性脑脊髓炎模型大鼠侧脑室注射嗅鞘细胞对髓鞘修复及运动功能的影响

BACKGROUND： Olfactory ensheathing cell transplantation can activate axonal regeneration and enhance myelin repair, which are beneficial for treating demyelinating diseases. OBJECTIVE： To explore the effects of olfactory ensheathing cell transplantation on myelin repair, synaptophysin expression, and motor function in a rat model of experimental allergic encephalomyelitis. DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed at the Laboratory of Provincial Hospital affiliated to Shandong University between August 2006 and September 2007. MATERIALS： Dibenzylamine （Hoechst 33342）, luxol fast blue, and rabbit anti-rat synaptophysin antibody were provided by Sigma, USA. METHODS： Olfactory ensheatbing cells extracted from neonatal Wistar rats were cultured for 10-14 days and labeled with dibenzylamine. Spinal cord extracted from a healthy guinea pig was homogenized and equally mixed with complete Freund＇s adjuvant; thereafter, the mixture was intracutaneously injected into two posterior voix pedis of healthy male Wistar rats to establish models of experimental allergic encephalomyelitis. Rats were randomly divided into a control encephalomyelitis group and an olfactory ensheathing cell transplantation group, 36 rats in each group. Physiological saline （2 μ L） or an olfactory ensheathing cell suspension （2 μ L） was separately injected along lateral cerebral ventricle at day 7 post-model induction. MAIN OUTCOME MEASURES： The migration and distribution of olfactory ensheathing cells were observed under fluorescence microscopy; myelin repair was detected using hematoxylin-eosin staining and luxol fast blue staining; synaptophysin expression was measured using immunohistochemical staining; motor function was evaluated using a motor function scale. RESULTS： Olfactory ensheatbing cells could survive in vivo and migrate to the distal end of the transplant focus and spinal cord, and survived 21 days. Hematoxylin-eosin staining and luxol fast blue staining indicated that myelin in the transplantation group was intact, and the inflammatory focus gradually disappeared. Transplantation increased synaptophysin expression （P 〈 0.05 versus control） and motor function （P 〈 0.05）. CONCLUSION： Olfactory ensheathing cell transplantation can promote myelin repair, increase synaptophysin protein expression, and ameliorate motor function in a rat model of experimental allergic encephalomyelitis.     

Progress in clinical trials of cell transplantation for the treatment of spinal cord injury:how many questions remain unanswered?

Spinal cord injury can lead to severe motor,sensory and autonomic nervous dysfunctions.However,there is currently no effective treatment for spinal cord injury.Neural stem cells and progenitor cells,bone marrow mesenchymal stem cells,olfactory ensheathing cells,umbilical cord blood stem cells,adipose stem cells,hematopoietic stem cells,oligodendrocyte precursor cells,macrophages and Schwann cells have been studied as potential treatments for spinal cord injury.These treatments were mainly performed in animals.However,subtle changes in sensory function,nerve root movement and pain cannot be fully investigated with animal studies.Although these cell types have shown excellent safety and effectiveness in various animal models,sufficient evidence of efficacy for clinical translation is still lacking.Cell transplantation should be combined with tissue engineering scaffolds,local drug delivery systems,postoperative adjuvant therapy and physical rehabilitation training as part of a comprehensive treatment plan to provide the possibility for patients with SCI to return to normal life.This review summarizes and analyzes the clinical trials of cell transplantation therapy in spinal cord injury,with the aim of providing a rational foundation for the development of clinical treatments for spinal cord injury.     

Olfactory ensheathing cells for spinal cord repair: crucial differences between subpopulations of the glia

<正>OECs for spinal cord repair:Is repairing the injured spinal cord by olfactory ensheathing cell(OEC)transplantation possible?A recent human trial in which a paralysed man regained some function after transplantation of partially purified OECs suggests that this therapy may be a successful approach(Tabakow et al.,2014).In another human trial in which olfactory mucosa lamina propria was transplanted,patients recovered     

嗅鞘细胞移植治疗脊髓损伤的临床验证

背景: 一系列基础研究证实在动物脊髓损伤的模型中,嗅鞘细胞移植能够促进脊髓损伤的再生和恢复脊髓的部分神经功能。部分临床实验证明嗅鞘细胞的移植的确能改善脊髓损伤患者的神经功能,从而改善其生活质量。 目的：验证嗅鞘细胞移植对脊髓损伤患者神经功能修复的作用及安全性。 方法：取流产胚胎嗅球并消化成为单个嗅鞘细胞,培养纯化2周左右,制成嗅鞘细胞悬液。选择脊髓损伤患者213例,全麻下将制备好的嗅鞘细胞悬液采用区域性多靶点注射方法移植于损伤脊髓的周围。采用ASIA量表对患者移植前1d及移植后3周~2个月进行评分,评价患者脊髓恢复状况。 结果与结论：所有患者的脊髓神经功能于术后3周均有不同程度的改变,脊髓功能评分及感觉与运动功能均较移植前明显提高(P < 0.001),且随时间延长呈不断改善趋势;最长患者随访5年,未见已恢复的神经功能 减退及移植不良反应。证实嗅鞘细胞移植对脊髓损伤患者的神经功能恢复有促进作用,可以部分恢复及改善其部分脊髓神经功能,且治疗方法安全。     

Olfactory ensheathing cell transplantation improves sympathetic skin responses in chronic spinal cord injury

Forty-three patients with chronic spinal cord injury for over 6 months were transplanted with bryonic olfactory ensheathing cells, 2-4 × 106, into multiple sites in the injured area under the sur-gical...     

嗅黏膜嗅鞘细胞与肌基膜管联合移植修复脊髓损伤

目的：观察嗅黏膜来源的嗅鞘细胞与肌基膜管联合移植后对脊髓损伤的修复效果。 方法：1只SD大鼠行背正中切口，顺椎旁肌纤维切除约1.5 cm×0.8 cm×0.6 cm的肌条，复温、漂洗并挤压肌条以排出肌浆，制成肌基膜管。4只SD大鼠麻醉后取出嗅黏膜，胶原酶消化法分离培养嗅鞘细胞，调整浓度至1011 L-1。取SD大鼠50只，随机分成5组：嗅鞘细胞+肌基膜管联合组、嗅鞘细胞组、肌基膜管组、模型组、正常组，10只/组。除正常组外，其余组均建立脊髓损伤模型，于T10横断脊髓并切除约2 mm，将培养7 d的嗅鞘细胞与肌基膜管按组别分别植入脊髓断端，模型组用浸有DMEM的凝胶海绵桥接横断的脊髓。 结果：移植后第8周，嗅鞘细胞+肌基膜管联合组、嗅鞘细胞组大鼠运动功能明显恢复，出现大关节大幅度运动，且前者运动功能BBB评分升高尤为显著（P < 0.01）；肌基膜管组大鼠仅见小关节轻微活动；模型组大鼠后肢挛缩重，无明显功能恢复。嗅鞘细胞+肌基膜管联合组后肢体感诱发电位及运动诱发电位的潜伏期显著低于其他各组（P < 0.01）。苏木精-伊红染色和核转录因子免疫组化染色结果显示，嗅鞘细胞+肌基膜管联合组、嗅鞘细胞组的移植物与损伤脊髓整合较好，未见明显空洞，有大量染色呈阳性的纤维，纤维较长，由近侧端长入远侧端；肌基膜管组有空洞形成，染色阳性的纤维数量少，纤维细小且排列紊乱；模型组端断间充满瘢痕组织，未见明显染色阳性纤维。 结论：嗅鞘细胞移植可促进脊髓损伤后的轴突再生，肌基膜管作为一种生物管道，两者联合应用可明显促进脊髓损伤后的轴突再生及功能恢复。     

接受嗅鞘细胞移植脊髓损伤大鼠电生理及后肢功能变化

背景：研究证实嗅鞘细胞有利于神经元存活,并可促进轴突再生。 目的：探讨嗅鞘细胞移植治疗大鼠脊髓损伤的效果。 方法：健康成年雌性SD大鼠40只,随机分为盐水对照组、细胞移植组,20只/组。另取10只SD大鼠用于嗅鞘细胞的分离培养。盐水对照组、细胞移植组大鼠均建立脊髓损伤模型,取双侧第8~10对肋间神经各2 cm,交叉植入脊髓缺损处(近端白质与远端灰质、远端白质与近端灰质),细胞移植组局部注射嗅鞘细胞2×106个,盐水对照组局部注射等量无菌生理盐水。通过体感诱发电位和运动诱发电位的检测,观察神经电生理恢复情况;BBB后肢运动功能评分结果;通过BDA顺行神经示踪,观察运动传导束恢复情况。 结果与结论：细胞移植组大鼠体感诱发电位及运动诱发电位的潜伏期、波幅明显优于盐水对照组(P < 0.01);细胞移植组大鼠BBB后肢运动功能评分较生理盐水组明显提高(P < 0.01);细胞移植组脊髓损伤区有较多BDA标记阳性神经纤维通过,其数量明显多于盐水对照组(P < 0.01)。证实局部注射嗅鞘细胞可以较好地恢复大鼠脊髓损伤后的神经电生理及后肢运动功能。     

Olfactory ensheathing cells from the nose: Clinical application in human spinal cord injuries

Olfactory mucosa, the sense organ of smell, is an adult tissue that is regenerated and repaired throughout life to maintain the integrity of the sense of smell. When the sensory neurons of the olfactory epithelium die they are replaced by proliferation of stem cells and their axons grow from the nose to brain assisted by olfactory ensheathing cells located in the lamina propria beneath the sensory epithelium. When transplanted into the site of traumatic spinal cord injury in rat, olfactory lamina propria or purified olfactory ensheathing cells promote behavioural recovery and assist regrowth of some nerves in the spinal cord. A Phase I clinical trial demonstrated that autologous olfactory ensheathing cell transplantation is safe, with no adverse outcomes recorded for three years following transplantation. Autologous olfactory mucosa transplantation is also being investigated in traumatic spinal cord injury although this whole tissue contains many cells in addition to olfactory ensheathing cells, including stem cells. If olfactory ensheathing cells are proven therapeutic for human spinal cord injury there are several important practical issues that will need to be solved before they reach general clinical application. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.     

Transplantation of olfactory ensheathing cells promotes axonal regeneration in a rat model of spinal cord injury

BACKGROUND:Transplantation of olfactory ensheathing cells (OECs) into the injured spinal cord has been shown to promote axonal regeneration and functional recovery.However,the mechanisms underlying the effects of OEC transplantation remain controversial.OBJECTIVE:To observe fibrotic scar formation and axonal regeneration in the damaged spinal cord following OEC transplantation,and to determine whether OEC transplantation promotes neural regeneration by attenuating fibrotic scar formation.DESIGN,TIME AND SETTING:A randomized,controlled animal experiment was performed at the Department of Developmental Morphology,Tokyo Metropolitan Institute for Neuroscience,Fuchu,Japan and at the Department of Human Anatomy,College of Basic Medical Sciences,China Medical University,China between April 2007 and May 2009.MATERIALS:OECs were obtained from olfactory nerves and olfactory bulbs of male,4-week-old,Sprague Dawley rats.Rabbit anti-serotonin polyclonal antibody,rabbit anti-calcitonin gene-related peptide polyclonal antibody,rabbit anti-glial fibrillary acidic protein polyclonal antibody,rabbit anti-type IV collagen polyclonal antibody,and mouse anti-rat endothelial cell antigen-1 monoclonal antibody were used.METHODS:Male,Sprague Dawley rats aged 8 weeks were randomly divided into three groups:sham-surgery (n = 3),surgery (n = 9),and OEC transplantation (n = 11).Spinal cord transection at the T9-10 level was performed and the rats were transplanted with a 2-μL (1 × 105 cells) cell suspension.MAIN OUTCOME MEASURES:Formation of glial and fibrotic scars was examined using immunohistochemistry for glial fibrillary acidic protein and type IV collagen.Serotonin-positive and calcitonin gene-related peptide-positive axons were visualized by immunohistochemistry,respectively.Double immunofluorescence for type IV collagen and rat endothelial cell antigen-1 was also performed to determine co-localization of type IV collagen deposition and blood vessels.RESULTS:At 1 week after spinal cord injury,numerous glial cells were observed around the lesion site.Formation of fibrotic scar was determined by a large amount of type IV collagen deposition in the lesion center,and descending serotonin- or ascending calcitonin gene-related peptideconiaining axons stopped at the fibrotic scar that was formed in the lesion site.At week after transplantation,the formation of fibrotic scar was significantly inhibited.In addition,the fibrotic structure was partly formed and centralized in the blood vessel,and serotonergic and calcitonin gene-related peptide-containing axons were regenerated across the lesion site.CONCLUSION:OEC transplantation into the injured spinal cord attenuated fibrotic scar formation and promoted axon regeneration.     

嗅鞘细胞移植脊髓损伤大鼠后Semaphorin3A的表达

脊髓损伤后损伤区Semaphorin3A(Sema3A)表达明显升高,嗅鞘细胞移植对此会有何影响？实验发现单纯脊髓横切损伤后,会出现脊髓出血、水肿、变性、坏死,囊腔形成,胶质细胞增生和神经纤维再生等病理反应。嗅鞘细胞移植后,脊髓的上述病理反应明显减轻,损伤区神经元和神经纤维的坏死程度下降,损伤区Sema3A表达降低。证实嗅鞘细胞移植可通过降低Sema3A表达对损伤脊髓神经元起保护作用。