Chronic transplantation of olfactory ensheathing cells promotes partial recovery after complete spinal cord transection in the rat

The goal of this study was to ascertain whether olfactory ensheathing cells (OECs) were able to promote axonal regeneration and functional recovery when transplanted 45 days after complete transection of the thoracic spinal cord in adult rats. OECs promoted partial restitution of supraspinal pathways evaluated by motor evoked potentials and modest recovery of hindlimb movements. In addition, OEC grafts reduced lumbar reflex hyperexcitability from the first month after transplantation. Histological results revealed that OECs facilitated corticospinal and raphespinal axons regrowth through the injury site and into the caudal spinal cord segments. Interestingly, raphespinal but not corticospinal fibers regenerated long distances through the gray matter and reached the lower lumbar segments (L5) of the spinal cord. However, delayed OEC grafts failed to reduce posttraumatic astrogliosis. In conclusion, the beneficial effects found in the present study further support the use of OECs for treating chronic spinal cord injuries.     

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.     

Protection of corticospinal tract neurons after dorsal spinal cord transection and engraftment of olfactory ensheathing cells

Transplantation of olfactory ensheathing cells (OECs) into the damaged rat spinal cord leads to directed elongative axonal regeneration and improved functional outcome. OECs are known to produce a number of neurotrophic molecules. To explore the possibility that OECs are neuroprotective for injured corticospinal tract (CST) neurons, we transplanted OECs into the dorsal transected spinal cord (T9) and examined primary motor cortex (M1) to assess apoptosis and neuronal loss at 1 and 4 weeks post-transplantation. The number of apoptotic cortical neurons was reduced at 1 week, and the extent of neuronal loss was reduced at 4 weeks. Biochemical analysis indicated an increase in BDNF levels in the spinal cord injury zone after OEC transplantation at 1 week. The transplanted OECs associated longitudinally with axons at 4 weeks. Thus, OEC transplantation into the injured spinal cord has distant neuroprotective effects on descending cortical projection neurons.     

Bone marrow mesenchymal stromal cells and olfactory ensheathing cells transplantation after spinal cord injury – a morphological and functional comparison in rats

Cell therapy for spinal cord injury (SCI) is a promising strategy for clinical application. Both bone marrow mesenchymal stromal cells (MSCs; also known as bone marrow‐derived ‘mesenchymal stem cells’) and olfactory ensheathing cells (OECs) have demonstrated beneficial effects following transplantation in animal models of SCI. However, due to the large number of affecting parameters that determine the therapy success and the lack of methodological consensus, the comparison of different works is difficult. Therefore, we compared the effects of MSC and OEC transplants at early or delayed time after a spinal cord contusion injury in the rat. Functional outcomes for locomotion, sensory perception and electrophysiological responses were assessed. Moreover, the grafted cells survival and the amount of cavity and spared tissue were studied. The findings indicate that grafted cells survived until 7 days post‐injection, but markedly disappeared in the following 2 weeks. Despite the low survival of the cells, MSC and OEC grafts provided tissue protection after early and delayed transplantation. Nevertheless, only acute MSC grafts improved locomotion recovery in treadmill condition and electrophysiological outcomes with respect to the other injured groups. These results, together with previous works, indicate that the MSC seem a better option than OEC for treatment of contusion injuries.     

低能激光照射嗅鞘细胞促进脊髓损伤大鼠神经功能的修复

BACKGROUND： Previous studies have demonstrated that low-power laser （LPL） irradiation can promote the regeneration of peripheral nerves and central nerves, as well as influence cellular proliferation. Therefore, it is thought to be a potential treatment for spinal cord injury. OBJECTIVE： Utilizing histological observations and behavioral evaluations, the aim of this study was to investigate the influence of transplanted olfactory ensheathing cells （OECs）, irradiated by LPL, on functional repair of rats following transversal spinal cord injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the animal experimental center in the First Affiliated Hospital of Xinjiang Medical University between January 2007 and February 2008. MATERIALS： A total of 52 Sprague Dawley rats were included in this experiment. Twelve rats were used to harvest OECs, some of which were irradiated by LPL on days 3, 5, and 7 in culture. The remaining 40 rats were used to establish T12 complete spinal cord transection injury. DMEM/F12 medium was purchased from Sigma, USA, Fluorogold was provided by Chemicon, USA, and the LY/JG650-D500-16 low-power laser was produced by Xi＇an Lingyue Electromechanical Science And Technology Co., Ltd., China. METHODS： The successful rat models were randomly divided into three groups： OEC transplantation, LPL-irradiated OEC transplantation, and control. These animals were microinjected with OEC suspension, LPL-irradiated OEC suspension, and DMEM/F12 medium （10μL） respectively 4 weeks after spinal cord was completely transected at the T12 level. MAIN OUTCOME MEASURES： Spinal cord injury was observed using hematoxylin-eosin staining Expression of nerve growth factor receptor p75 and glial fibrillary acidic protein were determined using immunohistochemical staining. Regeneration of spinal nerve fibers in rats was assayed by Fluorogold retrograde labeling method. Basso, Beattie and Bresnahan （BBB） scores were used to evaluate motor functions of rat lower limbs. RESULTS： Structural disturbances were observed following spinal cord injury in each group, and a large amount of scar tissue covered the broken ends, accompanied by porosis and inflammatory cell infiltration. Following OEC transplantation, the distal end connected to the proximal end. nerve growth factor receptor p75 and glial fibrillary acidic protein immunohistochemistry revealed positive OECs in the cephalad and caudal area of rats that received LPL-irradiated OEC transplantation. In the OECs group, only glial fibrillary acidic protein staining was observed. No staining was found in the control group. Neural fibers labeled with Fluorogold extended across the lesion area and into the cephalad and caudal area in the OECs and LPL-irradiated OECs groups, but were not present in the control group. BBB scores revealed statistically significant differences among the three groups （P 〈 0.05）： OECs irradiated by LPL group 〉 OECs group 〉 control group. CONCLUSION： Transplantation of OECs and LPL-irradiated OECs promoted functional repair in the injured spinal cord of rats, although LPL-irradiated OECs resulted in greater beneficial effects.     

嗅鞘细胞静脉移植治疗脊髓损伤

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。     

嗅鞘细胞移植治疗脊髓损伤的临床研究现状

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。     

Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs)

The prospects of achieving regeneration in the central nervous system (CNS) have changed, as most recent findings indicate that several species, including humans, can produce neurons in adulthood. Studies targeting this property may be considered as potential therapeutic strategies to respond to injury or the effects of demyelinating diseases in the CNS. While CNS trauma may interrupt the axonal tracts that connect neurons with their targets, some neurons remain alive, as seen in optic nerve and spinal cord (SC) injuries (SCIs). The devastating consequences of SCIs are due to the immediate and significant disruption of the ascending and descending spinal pathways, which result in varying degrees of motor and sensory impairment. Recent therapeutic studies for SCI have focused on cell transplantation in animal models, using cells capable of inducing axon regeneration like Schwann cells (SchCs), astrocytes, genetically modified fibroblasts and olfactory ensheathing glia cells (OECs). Nevertheless, and despite the improvements in such cell‐based therapeutic strategies, there is still little information regarding the mechanisms underlying the success of transplantation and regarding any secondary effects. Therefore, further studies are needed to clarify these issues. In this review, we highlight the properties of OECs that make them suitable to achieve neuroplasticity/neuroregeneration in SCI. OECs can interact with the glial scar, stimulate angiogenesis, axon outgrowth and remyelination, improving functional outcomes following lesion. Furthermore, we present evidence of the utility of cell therapy with OECs to treat SCI, both from animal models and clinical studies performed on SCI patients, providing promising results for future treatments.     

移植嗅鞘细胞可通过减弱纤维性瘢痕的产生而促进大鼠脊髓损伤后神经纤维的再生

背景：多项研究已证实嗅鞘细胞移植能促进脊髓损伤大鼠神经再生和功能的恢复,但嗅鞘细胞移植促进再生的分子机制还未完全阐明。 目的：观察嗅鞘细胞移植是否可以消除纤维性瘢痕的产生。 设计、时间及地点：对照随机动物实验,于2007年4月至2009年5月在日本东京都神经科学研究所发生形态部门和中国医科大学基础医学院解剖教研室完成。 材料：动物由日本东京都神经科学研究所动物管理及使用委员会提供 方法：选取体重为300-350克的SD大鼠23只,行胸椎9-10脊髓全横断,分为假手术对照组（n=3）、手术组（n=9）和嗅鞘细胞移植组（n=11）。嗅鞘细胞来源于未成熟的嗅球,并经过培养2-3周。 主要观察指标：分别应用GFAP和胶原IV蛋白免疫组化染色观察损伤部位胶质瘢痕和纤维性瘢痕的形成。脊髓内下行和上行的神经纤维束分别应用5-羟色胺和降钙素基因相关肽组化染色来观察。血管可用RECA-1染色来标识。同一切片上用RECA-1和胶原IV染色来比较血管的着色和胶原沉着的部位。 结果：在单纯的脊髓损伤组,损伤后一周的下行的5-羟色胺阳性纤维和上行的降钙素基因相关肽神经纤维均停止在纤维性瘢痕两端,在损伤部位周边有大量胶质细胞增生,损伤中心部位有大量胶原IV蛋白沉积而形成纤维性瘢痕。在损伤后同时移植嗅鞘细胞一周,5-羟色胺和降钙素基因相关肽阳性纤维均可见通过损伤部位。在损伤的脊髓节段,嗅鞘细胞移植组的阳性纤维均高于单纯损伤组。虽然移植组的损伤周边仍有大量的胶质细胞存在,但纤维性瘢痕却被显著的抑制。 结论：脊髓损伤过程中切断的神经纤维停止在纤维性瘢痕之前,移植嗅鞘细胞可以减弱纤维性瘢痕的产生而促进5-羟色胺阳性纤维越过脊髓损伤部位。     

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.     

Role of endogenous Schwann cells in tissue repair after spinal cord injury

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.     

人胚胎雪旺细胞脊髓内移植治疗晚期脊髓损伤

目的 采用人胚雪旺细胞移植治疗晚期脊髓损伤,并探讨其疗效及安全性。方法 显微镜下切除脊髓损伤节段增厚的瘢痕组织,松解粘连,切开囊腔或空洞。取人胚胎背根神经节,培养成雪旺细胞并贴附于可吸收薇乔3-0紫色线及薇乔网的载体上,然后将其移植到脊髓损伤部位。本组共治疗53例,其中男42例,女11例,年龄2～58岁,伤后时间为4个月～19年。结果 雪旺细胞移植后2～8w时随访,按美国脊髓损伤学会（ASIA）脊髓损伤神经功能分类国际标准评价,53例患者的脊髓功能均有部分恢复,其中运动功能由术前（41.49±15.83）分提高到术后（44.62±15.39）分,轻触觉由（57.89±22.87）分提高到（63.94±23.67）分,针刺觉由（55.96±20.99）分提高到（59.68±20.57）分。患者术后无脊髓感染、功能损伤加重及死亡等并发症。术后复查MRI示脊髓无瘤样增生及空洞扩大。结论 人胚雪旺细胞移植治疗晚期脊髓损伤安全可行,能促进晚期脊髓损伤患者脊髓神经功能的部分恢复。     

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.     

Comparative gene expression profiling of olfactory ensheathing cells from olfactory bulb and olfactory mucosa

Olfactory ensheathing cells (OEC) have the ability to promote regeneration in the nervous system. Hence, they hold promise for cell therapy. Most of the experimental studies have investigated the role of OECs taken from olfactory bulb (OB). However, for a clinical human application, olfactory mucosa (OM) seems to be the only acceptable source for OECs. Many studies have compared the distinct ability of OECs from OB and OM to improve functional nerve regeneration after lesion of the nervous system. Nevertheless, the two populations of OECs may differ in several points, which might affect all fate after transplantation in vivo. We report here the first study which compares gene expression profiling between these two populations of OECs. It appears that OB‐OECs and OM‐OECs display distinct gene expression pattern, which suggest that they may be implicated in different physiological processes. Notably, OM‐OECs overexpress genes characteristic of wound healing and regulation of extra cellular matrix. In contrast, OB‐OECs gene profile suggests a prominent role in nervous system development. Hence, OB‐OECs and OM‐OECs fundamentally differ in their gene expression pattern, which may represent a crucial point for future clinical application. © 2010 Wiley‐Liss, Inc.     

Transplantation of olfactory ensheathing cells or Schwann cells restores rapid and secure conduction across the transected spinal cord

Olfactory ensheathing cells (OECs) or Schwann cells were transplanted into the transected dorsal columns of the rat spinal cord to induce axonal regeneration. Electrophysiological recordings were obtained in an isolated spinal cord preparation. Without transplantation of cells, no impulse conduction was observed across the transection site; but following cell transplantation, impulse conduction was observed for over a centimeter beyond the lesion. Cell labelling indicated that the regenerated axons were derived from the appropriate neuronal source, and that donor cells migrated into the denervated host tract. As reported in previous studies, the number of regenerated axons was limited. Conduction velocity measurements and morphology indicated that the regenerated axons were myelinated, but conducted faster and had larger axon areas than normal axons. These results indicate that the regenerated spinal cord axons induced by cell transplantation provide a quantitatively limited but rapidly conducting new pathway across the transection site.     

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...     

Undesired effects of a combinatorial treatment for spinal cord injury--transplantation of olfactory ensheathing cells and BDNF infusion to the red nucleus

Transplantations of olfactory ensheathing cells (OECs) have been reported to promote axonal regeneration and functional recovery after spinal cord injury, but have demonstrated limited growth promotion of rat rubrospinal axons after a cervical dorsolateral funiculus crush. Rubrospinal neurons undergo massive atrophy after cervical axotomy and show only transient expression of regeneration-associated genes. Cell body treatment with brain-derived neurotrophic factor (BDNF) prevents this atrophy, stimulates regeneration-associated gene expression and promotes regeneration of rubrospinal axons into peripheral nerve transplants. Here, we hypothesized that the failure of rubrospinal axons to regenerate through a bridge of OEC transplants was due to this weak intrinsic cell body response. Hence, we combined BDNF treatment of rubrospinal neurons with transplantation of highly enriched OECs derived from the nasal mucosa and assessed axonal regeneration as well as behavioral changes after a cervical dorsolateral funiculus crush. Each treatment alone as well as their combination prevented the dieback of the rubrospinal axons, but none of them promoted rubrospinal regeneration beyond the lesion/transplantation site. Motor performance in a food-pellet reaching test and forelimb usage during vertical exploration (cylinder test) were more impaired after combining transplantation of OECs with BDNF treatment. This impaired motor performance correlated with lowered sensory thresholds in animals receiving the combinatorial therapy - which were not seen with each treatment alone. Only this combinatorial treatment group showed enhanced sprouting of calcitonin gene-related peptide-positive axons rostral to the lesion site. Hence, some combinatorial treatments, such as OECs with BDNF, may have undesired effects in the injured spinal cord.     

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.     

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.