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1.
中枢神经系统脱髓鞘是多发性硬化、脑自质营养不良及脊髓损伤的主要病理改变,导致神经系统功能缺失。动物实验中,将神经系统参与髓鞘形成的细胞植入脱髓鞘部位,取得了一定的冶疗效果。目前用于移植的细胞主要有少突胶质细胞前体细胞、雪旺细胞、嗅球成髓鞘细胞等。随着近年来对神经干细胞研究的不断深入,少突胶质细胞前体细胞被认为是最有前途的供体细胞。不足之处在于对于成年慢性脱髓鞘动物模型移植后的复髓鞘程度的定量描述非常有限,有待于进一步研究。  相似文献   

2.
脊髓损伤是一种严重危害人类健康的疾病,因其少突胶质细胞不能形成轴突迁移引导的通道,并分泌抑制因子,以及星形胶质细胞在损伤区快速反应性增生形成胶质瘢痕,抑制轴突的生长,使脊髓损伤的治疗成为目前医学领域的一个棘手问题。嗅鞘细胞具有良好的轴突再生和准确形成靶特异性突轴连接的能力;低能激光照射对神经系统及嗅鞘细胞的作用包括,保留甚至促进受损神经元的活性,减少瘢痕的形成,阻止神经元的退行性改变,又能通过干拢一些因素而增强嗅鞘细胞的活性。嗅鞘细胞移植及低能激光照射在脊髓损伤的修复中具有重要的作用。  相似文献   

3.
目的:对嗅鞘细胞生物学特性、培养纯化、嗅鞘细胞移植的可能机制及嗅鞘细胞移植在临床的应用等方面进行分析,介绍嗅鞘细胞移植治疗脊髓损伤的研究现状。 资料来源:以olfactory ensheathing cells,spinal cord injury,嗅鞘细胞,脊髓损伤为检索词检索PubMed数据库(2000/2009),中国期刊全文数据库(2000/2009)。 资料选择:纳入标准:①文章所述内容应与嗅鞘细胞及脊髓损伤密切相关。②同一领域选择近期发表或在权威杂志上发表的文章。排除标准:①重复性研究。②Meta分析。 结局评价指标:嗅鞘细胞移植治疗脊髓损伤的研究进展。 结果:嗅鞘细胞具有与许旺细胞和星形胶质细胞相似的特征。目前嗅鞘细胞移植的动物实验主要致力于提高轴突再生能力、替代细胞成分、阻止脱髓鞘病变和促进髓鞘再生等方面,移植的嗅鞘细胞具有促进感觉及运动功能恢复的客观结果,有些移植研究甚至已经进入了临床试验阶段。不过嗅鞘细胞移植由动物实验转化到临床应用还受到很多因素的影响,诸如移植剂量、细胞生长因子的活力,细胞移植的风险等,尤其是嗅鞘细胞移植后的近期及远期效果还需要进一步深入研究、评价,并且需要长时间的随访。有研究已经把用基因转染的嗅鞘细胞用于移植,在动物试验身上已经取得了满意的效果。 结论:随着基因工程技术发展以及嗅鞘细胞移植修复神经机制的深入研究,嗅鞘细胞移植必将为临床治疗脊髓损伤的患者带来康复的希望。  相似文献   

4.
背景:脊髓损伤后神经功能难以自行恢复,嗅鞘细胞具有外周性和中枢性两种胶质细胞的成鞘功能,是修复受损神经最有前途的种子细胞。嗅鞘细胞移植到受损脊髓后的组织学和超微结构的变化可能帮助解释嗅鞘细胞发挥修复作用的机制。 目的: 验证嗅球源性嗅鞘细胞移植对脊髓损伤功能恢复的促进作用,并观察移植的嗅鞘细胞对神经元和轴突组织和超微结构的影响。 方法:将已制备脊髓模型的Wistar大鼠随机分为3组,对照组不做任何注射操作,DMEM/F12组注射DMEM/F12培养基,嗅鞘细胞组注射嗅鞘细胞悬液。每周进行肢体活动BBB评分,8周后取脊髓标本进行组织学和免疫组织化学观察,评价脊髓损伤的修复情况,并观察嗅鞘细胞移植对脊髓组织和超微结构的影响。 结果与结论:3组动物均出现后肢运动功能的恢复,嗅鞘细胞组优于对照组和DMEM/F12组,在4周后更为明显。组织学观察可见,在嗅鞘细胞组可见有神经纤维通过损伤处。损伤处附近,嗅鞘细胞组脊髓腹侧的神经纤维和神经元形态较好,损伤较轻。而对照组和DMEM/F12组神经纤维和神经元损害严重。嗅鞘细胞组的caspsase-3阳性细胞数少于对照组和DMEM/F12组。超微结构观察可见,嗅鞘细胞组的神经纤维和细胞形态均优于对照组和DMEM/F12组。结果表明嗅鞘细胞移植对大鼠脊髓损伤修复有明显的促进作用,并可恢复损伤神经的部分功能,对受损神经纤维和神经元有保护作用。  相似文献   

5.
背景:嗅鞘细胞是介于星形胶质细胞和许旺细胞之间的一类特殊的胶质细胞,具有切实有效的促进神经再生修复的作用,但其相关机制还没确定。 目的:观察嗅球成鞘细胞移植对脊髓慢性压迫损伤后脊髓功能形态和脑源性神经营养因子的影响,以及嗅鞘细胞移植后脊髓慢性压迫损伤动物脊髓功能的修复。 设计、时间及地点:对照动物实验,细胞学观察,于2005-11/2007-03在上海中医药大学脊柱病研究所完成。 材料:新生SD雄性大鼠采用酶消化法培养原代大鼠嗅鞘细胞,并将其制成细胞悬液。雄性3月龄SD大鼠以螺钉持续性压迫大鼠C4脊髓建立脊髓慢性压迫动物模型。 方法:造模后大鼠分为模型组、嗅鞘细胞组、DMEM/Ham’s F-12 培养液组、正常组,每组12只。嗅鞘细胞组在距离脊髓压迫区域上下0.5 mm处选4点注射,按1μL/点脊髓内注射109 L-1嗅鞘细胞,注入速度为1μL/ min。 主要观察指标:应用光学显微镜、电子显微镜观察脊髓形态的变化,采用免疫组织化学、PT-PCR 的方法检测脊髓组织脑源性神经营养因子的分泌,以改良的Gale联合行为评分法对脊髓功能进行评定, 结果:免疫组织化学检测显示,嗅鞘细胞移植能部分改善大鼠脊髓灰质神经细胞的凋亡程度,延缓白质神经纤维的减少,促进髓鞘的修复与再生。与模型组、DMEM/Ham’s F-12 培养液组比较, 嗅鞘细胞移植治疗后脊髓组织中脑源性神经营养因子表达明显增加(P < 0.01)。与模型组、DMEM/Ham’s F-12 培养液组比较,嗅鞘细胞移植能较大程度的改善大鼠脊髓功能(P < 0.05)。 结论:嗅鞘移植能够部分改善脊髓损伤后脊髓组织的病理形态,促进脊髓组织中脑源性神经营养因子的表达,减轻脊髓慢性压迫后的功能损害。  相似文献   

6.
摘要:嗅鞘细胞是一种特殊类型的神经胶质细胞,起源于嗅基底膜,分布在嗅球、嗅神经,并可伴随嗅神经轴突迁徙入脑。尽管目前嗅鞘细胞移植技术治疗脊髓损伤的疗效已经被大量基础实验证实,并且已经开始了初步的临床试验,但其在移植后作用的主要机制仍然需要继续探讨。脊髓的再生与修复是一个非常复杂的过程, 目前还有许多问题有待解决, 如嗅鞘细胞移植治疗的主要机制、嗅鞘细胞移植时机的选择、嗅鞘细胞纯度对移植效果的影响、嗅鞘细胞植入的方法等。  相似文献   

7.
背景:对于脊髓损伤,目前临床尚无有效的治疗对策,近年来嗅鞘细胞移植治疗脊髓损伤修复取得了一定的进展。NG2是主要的硫酸软骨素蛋白多糖分子,对轴突有抑制作用。 目的:观察嗅鞘细胞移植对脊髓损伤大鼠NG2表达的影响,进一步分析嗅鞘细胞移植在修复脊髓损伤中的作用途径。 方法:将112只大鼠随机分为4组,空白组、模型组、嗅鞘细胞移植组及DF12组各28只。空白组仅切开T10全椎板及T9,T11部分椎板,对脊髓未作其他处理;其他3组应用脊髓横切法制作脊髓损伤动物模型。嗅鞘细胞移植组进行嗅鞘细胞移植,每侧断端植入20 000 cells;DF12组于相同部位注射DF12培养液。在大鼠脊髓损伤后1,3,7,14,28,42和56 d时,取材按照SP试剂盒的操作步骤检测NG2的表达。 结果与结论:空白组NG2呈低表达,在模型组、DF12组脊髓损伤24 h后损伤部位的NG2的表达开始升高,7 d时达到顶点,4周时NG2表达明显降低,6,8周时仅在局部有所表达。嗅鞘细胞移植组脊髓损伤1 d时NG2表达开始增加,主要在损伤部位,在各时间点与模型组、DF12组相比NG2表达水平明显降低,但高于空白组NG2各时间点的表达。提示嗅鞘细胞移植后NG2的表达水平降低,嗅鞘细胞具有抑制NG2表达的作用,可消除或减轻细胞外基质中对轴突有抑制作用的化学屏障,这可能是其治疗脊髓损伤促进轴突再生的机制之一。  相似文献   

8.
背景:嗅鞘细胞移植治疗脊髓损伤在众多疗法中效果较佳,成为最有前景的治疗方法之一。目前移植方法为局部移植,存在操作复杂、创伤大、重复移植治疗困难等缺点。寻找一种简单易行且疗效好的移植方法成为各国学者研究的热点。 目的:分析嗅鞘细胞静脉移植治疗脊髓损伤的可行性和疗效。 方法:制备Wistar大鼠脊髓半切模型,随机分4组:嗅鞘细胞髓内局部移植组、嗅鞘细胞静脉移植组、D/F12静脉移植组和空白对照组。定期行CBS功能评分及组织学检查,评价脊髓修复情况。 结果与结论:嗅鞘细胞髓内局部移植组、嗅鞘细胞静脉移植组的功能恢复和组织学改变优于D/F12静脉移植组和空白对照组,嗅鞘细胞髓内局部移植组、嗅鞘细胞静脉移植组间无显著差别。说明嗅鞘细胞静脉移植可向脊髓损伤部位迁移并修复脊髓损伤,其疗效与嗅鞘细胞髓内局部移植相当。  相似文献   

9.
背景:对于脊髓损伤,目前临床尚无有效的治疗对策,近年来嗅鞘细胞移植对脊髓损伤修复取得了一定的进展。 目的:观察嗅鞘细胞移植在缓解损伤脊髓的病理反应和超微结构变化,及其在发生发展中的作用。 方法:60只大鼠随机分为空白组,模型组,嗅鞘胞移植组和DF12组,每组15只。空白组:仅切开T10全椎板及T9,T11部分椎板,对脊髓未作其他处理,明胶海绵轻柔压迫止血;模型组:仅切断脊髓,未作特殊处理;嗅鞘细胞移植组和DF12组:切断脊髓后用微量注射器分别注射嗅鞘细胞和DF12培养液,随后缝合切口。脊髓损伤后1,3,7,14,28,42,56 d每组麻醉2只受检大鼠,取材做光镜观察和电镜观察。 结果与结论:单纯脊髓横切损伤后,发生了出血、水肿、变性、坏死以及囊腔形成,胶质细胞增生和神经纤维再生。嗅鞘细胞移植后,明显减轻了神经元和神经纤维的坏死变性程度,减轻病理反应,并能对损伤神经元实施保护;防止了胶质细胞过度增生形成瘢痕屏障,明显增加了再生神经纤维的数量。提示嗅鞘细胞移植对损伤脊髓具有减轻病理反应和促进修复的作用。  相似文献   

10.
嗅鞘细胞移植治疗脊髓损伤的临床验证   总被引:1,自引:0,他引:1  
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。  相似文献   

11.
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.  相似文献   

12.
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.  相似文献   

13.
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.  相似文献   

14.
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。  相似文献   

15.
Ibanez C  Ito D  Zawadzka M  Jeffery ND  Franklin RJ 《Glia》2007,55(2):144-151
Olfactory ensheathing cells (OECs), the principal glial cells of the peripheral olfactory system, have many phenotypic similarities with Schwann cells of the peripheral nervous system. This makes reliably distinguishing these two cells types difficult, especially following transplantation into areas of injury in the central nervous system. In an attempt to identify markers by which these two cells types can be distinguished, a recent proteomic analysis of fetal OECs and adult Schwann cells identified the actin-binding protein calponin as a potential marker expressed by OECs but not Schwann cells. Since many studies designed with the translational goal of autologous transplantation in mind have used adult OECs, this study examined the expression of calponin by adult OECs, both in vivo within the peripheral olfactory system and in vitro. Calponin colocalized with strongly fibronectin positive fibroblasts in the olfactory mucosa (OM) and meningeal cells in the olfactory bulb (OB) but not with S100beta or neuropeptide-Y positive OECs. In tissue culture, calponin was strongly expressed by fibronectin-expressing fibroblasts from OM, sciatic nerve and skin and by meningeal cells from the OB, but not by p75(NTR)- and S100beta-expressing OECs. These data, supported by Western blotting, indicate that calponin can not be used to distinguish adult OECs and Schwann cells.  相似文献   

16.
Although it was once thought that the central nervous system (CNS) of mammals was incapable of substantial recovery from injury, it is now clear that the adult CNS remains responsive to various substances that can promote cell survival and stimulate axonal growth. Among these substances are growth factors, including the neurotrophins and cytokines, and growth-supportive cells such as Schwann cells, olfactory ensheathing glia, and stem cells. We review the effects of these substances on promoting axonal growth after spinal cord injury, placing particular emphasis on the genetic delivery of nervous system growth factors to specific sites of injury as a means of promoting axonal growth and, in limited instances, functional recovery.  相似文献   

17.
Among the possible sources of autologous cells and tissues for use in spinal cord injury grafts, one promising source is the olfactory mucosa containing olfactory ensheathing cells and neural progenitor cells. Olfactory mucosa transplantation for spinal cord injury has been effective in animal models and in pilot clinical trials. However, the contributions of olfactory ensheathing cells and neurons in olfactory mucosa are unclear. For the present study, we prepared primary olfactory mucosal cells and used a cortex–Matrigel coculture assay system to examine the axonal outgrowth of olfactory mucosa. Axonal outgrowth from cortical slices was significantly enhanced in olfactory mucosal cells compared with noncell controls and respiratory mucosal cells, which have few olfactory ensheathing cells and neurons. Axonal outgrowth was severely reduced after treatment with an antineurotrophin cocktail. A conditioned medium in the olfactory mucosa‐derived cell group contained neurotrophin‐3. Some olfactory ensheathing cells and almost all neurons were immunopositive for neurotrophin‐3. Axons originating from cortical slices targeted mainly the astrocyte‐like olfactory ensheathing cells. Our findings demonstrate that the axonal outgrowth effect of olfactory mucosa is supported by both olfactory ensheathing cells and neurons in olfactory mucosa. © 2014 Wiley Periodicals, Inc.  相似文献   

18.
Schwann cells are glial cells of peripheral nervous system, responsible for axonal myelination and ensheathing, as well as tissue repair following a peripheral nervous system injury. They are one of several cell types that are widely studied and most commonly used for cell transplantation to treat spinal cord injury, due to their intrinsic characteristics including the ability to secrete a variety of neurotrophic factors. This mini review summarizes the recent findings of endogenous Schwann cells after spinal cord injury and discusses their role in tissue repair and axonal regeneration. After spinal cord injury, numerous endogenous Schwann cells migrate into the lesion site from the nerve roots, involving in the construction of newly formed repaired tissue and axonal myelination. These invading Schwann cells also can move a long distance away from the injury site both rostrally and caudally. In addition, Schwann cells can be induced to migrate by minimal insults (such as scar ablation) within the spinal cord and integrate with astrocytes under certain circumstances. More importantly, the host Schwann cells can be induced to migrate into spinal cord by transplantation of different cell types, such as exogenous Schwann cells, olfactory ensheathing cells, and bone marrow-derived stromal stem cells. Migration of endogenous Schwann cells following spinal cord injury is a common natural phenomenon found both in animal and human, and the myelination by Schwann cells has been examined effective in signal conduction electrophysiologically. Therefore, if the inherent properties of endogenous Schwann cells could be developed and utilized, it would offer a new avenue for the restoration of injured spinal cord.  相似文献   

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