Optimal time for subarachnoid transplantation of neural progenitor cells in the treatment of contusive spinal cord injury

This study aimed to identify the optimal neural progenitor cell transplantation time for spinal cord injury in rats via the subarachnoid space. Cultured neural progenitor cells from 14-day embryonic rats, constitutively expressing enhanced green fluorescence protein, or media alone, were injected into the subarachnoid space of adult rats at 1 hour (acute stage), 7 days (subacute stage) and 28 days (chronic stage) after contusive spinal cord injury. Results showed that grafted neural progenitor cells migrated and aggregated around the blood vessels of the injured region, and infiltrated the spinal cord parenchyma along the tissue spaces in the acute stage transplantation group. However, this was not observed in subacute and chronic stage transplantation groups. O4- and glial fibrillary acidic protein-positive cells, representing oligodendrocytes and astrocytes respectively, were detected in the core of the grafted cluster attached to the cauda equina pia surface in the chronic stage transplantation group 8 weeks after transplantation. Both acute and subacute stage transplantation groups were negative for O4 and glial fibrillary acidic protein cells. Basso, Beattie and Bresnahan scale score comparisons indicated that rat hind limb locomotor activity showed better recovery after acute stage transplantation than after subacute and chronic transplantation. Our experimental findings suggest that the subarachnoid route could be useful for transplantation of neural progenitor cells at the acute stage of spinal cord injury. Although grafted cells survived only for a short time and did not differentiate into astrocytes or neurons, they were able to reach the parenchyma of the injured spinal cord and improve neurological function in rats. Transplantation efficacy was enhanced at the acute stage in comparison with subacute and chronic stages.     

甲基强的松龙和神经干细胞移植联合治疗大鼠脊髓损伤

目的：观察甲基强的松龙和神经干细胞移植对大鼠脊髓损伤后神经结构修复和功能恢复的治疗作用并探讨其作用机制。方法：制备大鼠胸10脊髓损伤模型，体外培养、诱导分化大鼠神经干细胞，定量评价甲基强的松龙和神经干细胞移植对脊髓损伤后神经结构修复和功能恢复的影响。结果：与对照组相比，移植组明显地增强了生长相关蛋白（GAP－43）mRNA的表达，促进了乙酰胆碱转移酶（ChAT)阳性脊髓运动神经元的再生、神经结构的修复和下肢运动功能的恢复（P＜0．05）。结论：甲基强的松龙和神经干细胞移植通过增强GAP－43 mRNA的表达、运动神经元的再生而促进了脊髓损伤后神经结构的修复和功能的恢复，是急性脊髓损伤的一种有效的治疗方案。     

不同来源成体神经干细胞促进大鼠脊髓损伤功能修复的比较研究

目的 评价大脑、骨髓和脂肪组织3种不同来源的神经干细胞对大鼠脊髓挫伤的治疗效果.方法 选取来源于同一大鼠成体中大脑、骨髓和脂肪的3个部位的组织,分离、诱导分化为不同来源的神经干细胞;应用自由落体损伤模型装置造成大鼠脊髓挫伤.将不同来源的神经干细胞分别移植入大鼠脊髓损伤部位,通过BBB评分比较修复脊髓损伤功能的效果,应用免疫荧光染色检测不同移植细胞在损伤脊髓中的存活、分布、迁移的情况.另设假手术对照组和生理盐水对照组.结果 与假手术对照组和生理盐水对照组比较,3个细胞处理组BBB评分在2～8周开始增加,9周以后更加明显,差异开始有统计学意义(P<0.05).在移植后1周和4周,细胞移植组中脑源性神经干细胞(SVZ-NSs)组Brdu/nestin+>神经元存活的数目明显高于其他2组.但差异没有统计学意义(P>0.05);到了第8周,3组均仅有少量Brdu/nestin+>细胞存活,相互之间比较差异无统计学意义(P>0.05).结论 植入来源于大脑、骨髓和脂肪组织的神经干细胞都可以在一定程度上提高脊髓损伤后运动功能恢复,但SVZ-NSs组的脊髓损伤大鼠运动功能恢复要比脂肪来源的神经干细胞(AD-NSs)组及骨髓来源的神经干细胞(BM-NSs)组更好.AD-NSs由于来源广泛和强有力的增殖能力,相比其他来源的神经干细胞,可能是更好的选择.     

Transplantation of placenta-derived mesenchymal stem cell-induced neural stem cells to treat spinal cord injury

Because of their strong proliferative capacity and multi-potency, placenta-derived mesenchymal stem cells have gained interest as a cell source in the field of nerve damage repair. In the present study, human placenta-derived mesenchymal stem ceils were induced to differentiate into neural stem cells, which were then transplanted into the spinal cord after local spinal cord injury in rats. The motor functional recovery and pathological changes in the injured spinal cord were observed for 3 successive weeks. The results showed that human placenta-derived mesenchymal stem cells can differentiate into neuron-like cells and that induced neural stem cells contribute to the restoration of injured spinal cord without causing transplant rejection. Thus, these cells promote the recovery of motor and sensory functions in a rat model of spinal cord injury. Therefore, human placenta-derived mesenchymal stem cells may be useful as seed cells during the repair of spinal cord injury.     

Grafted lineage-restricted precursors differentiate exclusively into neurons in the adult spinal cord

Multipotent neural stem cells (NSCs) have the potential to differentiate into neuronal and glial cells and are therefore candidates for cell replacement after CNS injury. Their phenotypic fate in vivo is dependent on the engraftment site, suggesting that the environment exerts differential effects on neuronal and glial lineages. In particular, when grafted into the adult spinal cord, NSCs are restricted to the glial lineage, indicating that the host spinal cord environment is not permissive for neuronal differentiation. To identify the stage at which neuronal differentiation is inhibited we examined the survival, differentiation, and integration of neuronal restricted precursor (NRP) cells, derived from the embryonic spinal cord of transgenic alkaline phosphatase rats, after transplantation into the adult spinal cord. We found that grafted NRP cells differentiate into mature neurons, survive for at least 1 month, appear to integrate within the host spinal cord, and extend processes in both the gray and white matter. Conversely, grafted glial restricted precursor cells did not differentiate into neurons. We did not observe glial differentiation from the grafted NRP cells, indicating that they retained their neuronal restricted properties in vivo. We conclude that the adult nonneurogenic CNS environment does not support the transition of multipotential NSCs to the neuronal commitment stage, but does allow the survival, maturation, and integration of NRP cells.     

神经干细胞移植修复鼠脊髓损伤的实验研究

目的 :观察神经干细胞移植治疗对鼠脊髓损伤后神经结构修复和功能恢复的作用并探讨其作用机制。方法 :制备鼠T10 脊髓损伤模型 ,体外培养、诱导鼠神经干细胞 ,定量评价神经干细胞移植对脊髓损伤后神经结构修复和功能恢复的影响。结果 :与对照组相比 ,神经干细胞移植组明显的增强了GAP 43mRNA的表达 ,促进了脊髓ChAT阳性的运动神经元的再生、结构的修复和下肢运动功能的恢复。结论 :神经干细胞移植促进了脊髓损伤后神经结构的修复和功能的恢复 ,是急性脊髓损伤一种有效的治疗方案     

骨髓间充质干细胞立体定向移植治疗大鼠脊髓损伤*

摘要 背景：传统观念认为,神经组织损伤后几乎不能再生,以往对SCI的治疗缺乏有效手段,致使本病致残率高,疗效差。干细胞治疗关键在于移植具有再生能力的干细胞,通过多种作用机制,可以重建中枢神经系统的结构和功能,近年来引起了广泛的关注。 目的：探讨立体定向移植骨髓间充质干细胞（MSCs）对大鼠脊髓损伤修复的影响并探讨其机制 设计、时间及地点：随机对照动物实验,于2007-10/2008-6在天津市环湖医院完成。 材料：1月龄SD大鼠20只,用于制备骨髓间充质干细胞;健康成年Wistar大鼠45只,雌性、同系,体质量280±20 g。将动物随机分为对照组、假手术组与移植组,每组各15只。 方法：密度梯度离心法结合贴壁筛选法分离骨髓间充质干细胞,经流式细胞仪鉴定为MSCs。以动脉瘤夹夹闭法制备大鼠脊髓损伤（SCI）模型,在SCI大鼠致伤后第7天,通过立体定向途径移植MSCs到移植组大鼠脊髓损伤中心,移植等量生理盐水至假手术组大鼠脊髓损伤中心,对照组大鼠不做处理。 主要观察指标：SCI大鼠损伤前及损伤后第7天、14天、30天、60天、90天的BBB评分;损伤后第90天处死大鼠,观察其脊髓组织中有无BrdU阳性细胞、Brdu+NSE、Brdu+GFAP、Brdu+bFGF、Brdu+BDNF免疫组化双染阳性细胞并观察NSE、GFAP、bFGF、BDNF单染阳性细胞。 结果： ①BBB评分发现,MSCs移植组大鼠BBB后肢功能评分恢复优于对照组（p<0.05）;假手术组BBB评分在损伤后30天内恢复速度慢于对照组（p<0.05）,至第90天与对照组比较无显著差异（P>0.05）;②免疫组织化学染色发现,移植组大鼠脊髓内在损伤中心及头、尾端距离脊髓损伤中心1cm处均可见BrdU染色阳性细胞及Brdu+NSE、Brdu+GFAP、Brdu+bFGF、Brdu+BDNF免疫组化双染阳性细胞。移植组NSE、GFAP、bFGF、BDNF单染阳性细胞数明显高于对照组和假手术组（p<0.05）。 结论： MSCs移植可以促进SCI大鼠的神经功能的恢复,其机制可能与移植细胞分化为神经元样和神经胶质细胞样细胞,并分泌或促进宿主分泌神经营养因子有关。 关键词 脊髓损伤 骨髓间充质干细胞 立体定向 细胞移植     

间充质干细胞移植修复脊髓损伤的研究现状

骨髓间充质干细胞在体外没有外界因素作用下连续传50代仍可保持原来的特性,亦可在一些条件的诱导下分化成神经细胞。实验研究表明,间充质干细胞移植能促进脊髓损伤的神经结构修复及神经功能恢复,其机制可能与替代作用、营养作用、诱导作用、桥接作用等有关。携带外源功能基因的骨髓间充质干细胞移植到体内存活、迁徙、分化并基因表达脑源性生长因子、神经生长因子等细胞因子,明显促进脊髓损伤的恢复,成为了新的研究热点。随着对间充质干细胞的生物学特性进一步深入研究,一些未解决的问题将会逐步得到解决,为脊髓损伤和其他神经系统疾病的患者带来新的希望。     

Neurally induced umbilical cord blood cells modestly repair injured spinal cords

Umbilical cord blood (UCB) is known to have stem/progenitor cells. We earlier showed that novel progenitors could be isolated from cryopreserved human UCB with high efficiency. The multipotent progenitor cells were induced to differentiate into neural-lineage cells under the appropriate condition. In this study, we confirmed these neurally induced progenitor cells (NPCs), containing higher quantities of nerve growth factor, promoted functional recovery in rats with spinal cord injury (SCI). Sprague-Dawley rats with SCI achieved a modest improvement in locomotor rating scale until 10 weeks after transplantation of the NPCs. SCI rats treated with NPCs also showed somatosensory-evoked potentials were recovered, and grafted cells especially exhibited oligodendrocytic phenotype around the necrotic cavity. These findings suggest that UCB-NPCs might be a therapeutic resource to repair damaged spinal cords.     

再程序化脂肪干细胞移植治疗大鼠脊髓损伤的机制

目的制备再程序化脂肪干细胞(ADSCs),并在体研究再程序化ADSCs移植入大鼠脊髓损伤模型后促进损伤脊髓神经功能恢复的作用和机制。方法体外培养、纯化和鉴定大鼠ADSCs,并利用慢病毒包装神经元生成素2(Ngn2)基因转染ADSCs制备再程序化干细胞。体内实验将48只雌性SD大鼠随机分成3组:SCI对照(A)组、单纯ADSCs移植(B)组和Ngn2-ADSCs移植(C)组。采用BBB评分评价大鼠运动功能,并通过HE染色、免疫组化和免疫荧光等方法检测脊髓组织学改变和相关蛋白的表达水平,进而观察实验动物脊髓功能恢复情况。结果 Ngn2-ADSCs移植组在运动功能评分、胶质瘢痕的形成、脊髓损伤后病理变化和分泌神经营养因子BDNF和VEGF蛋白含量明显优于其他组。结论 Ngn2-ADSCs移植后能有效地存活,并分化为神经细胞,抑制胶质瘢痕形成,减小脊髓损伤空洞,增加BDNF和VEGF表达,最终促进SCI大鼠的运动功能恢复,较单纯应用ADSCs能更好地促进SCI修复。     

人脐带间充质干细胞移植对大鼠脊髓损伤神经功能恢复的评价

目的 观察人脐带间充质干细胞（human umbilical cordmesenchymal stem cell，hUCMSC）移植对大鼠脊髓损伤神经功能恢复的影响。方法 SD大鼠70只，随机分为3组：脊髓半切＋hUCMSC组（n=30）、脊髓半切＋PBS组（n=30）和假手术组（n=10）。脊髓半切＋hUCMSC组和PBS组又分为头侧注射、尾侧注射和头尾两侧注射三个亚组。移植后1、7、14、21、28d观察大鼠神经功能恢复情况，应用免疫组化检测移植到脊髓的hUCMSC胶质纤维酸性蛋白（GFAP）和神经元特异性烯醇化酶（NSE）表达情况。结果 大鼠脊髓半切损害后，hUCMSC组动物较PBS组有明显的神经功能恢复。植入后28d在宿主脊髓中存活的hUCMSC细胞MABl281（mouse antiuman nuclei monoclonal antibody）染色阳性，免疫组化双标染色显示MABl28l阳性细胞亦分别有NSE或GFAP表达并向损伤部位迁移，hUCMSC来源的GFAP阳性细胞可见明显的树突生长。结论 hUCMSC移植到宿主损伤脊髓后可以存活、向损伤部位迁移，并向神经元样和星形胶质细胞分化，且可促进大鼠脊髓损伤后神经功能恢复。hUCMSC作为一种来源广泛的干细胞用于治疗脊髓损伤可能具有重要的价值。     

Adult neural progenitor cells provide a permissive guiding substrate for corticospinal axon growth following spinal cord injury

Adult neural progenitor cells (NPC) are an attractive source for cell transplantation and neural tissue replacement after central nervous system (CNS) injury. Following transplantation of NPC cell suspensions into the acutely injured rat spinal cord, NPC survive; however, they migrate away from the lesion site and are unable to replace the injury-induced lesion cavity. In the present study we examined (i) whether NPC can be retained within the lesion site after co-transplantation with primary fibroblasts, and (ii) whether NPC promote axonal regeneration following spinal cord injury. Co-cultivation of NPC with fibroblasts demonstrated that NPC adhere to fibroblasts and the extracellular matrix produced by fibroblasts. In the presence of fibroblasts, the differentiation pattern of co-cultivated NPC was shifted towards glial differentiation. Three weeks after transplantation of adult spinal-cord-derived NPC with primary fibroblasts as mixed cell suspensions into the acutely injured cervical spinal cord in adult rats, the lesion cavity was completely replaced. NPC survived throughout the graft and differentiated exclusively into glial cells. Quantification of neurofilament-labeled axons and anterogradely labeled corticospinal axons indicated that NPC co-grafted with fibroblasts significantly enhanced axonal regeneration. Both neurofilament-labeled axons and corticospinal axons aligned longitudinally along GFAP-expressing NPC-derived cells, which displayed a bipolar morphology reminiscent of immature astroglia. Thus, grafted astroglial differentiated NPC promote axon regrowth following spinal cord injury by means of cellular guidance.     

骨髓间质干细胞移植对大鼠脊髓损伤神经功能恢复的影响

目的：观察成人骨髓间质干细胞（hBMSCs)移植对大鼠脊髓损伤神经功能恢复的影响.方法：Wistar大鼠90只，随机分为脊髓半切＋hBMSCs组、脊髓半切＋PBS组、单纯脊髓半切组和假手术组。脊髓半切＋hBMSCs组和PBS组又分别分为头侧注射、尾侧注射和头尾两侧注射三个亚组。移植后1、7、14、21、28d观察大鼠神经功能恢复情况，应用免疫组化和免疫荧光技术检测BrdU标记hBMSCs的胶质纤维酸性蛋白（GFAP）和神经元特异性核蛋白（NeuN)表达情况。结果：大鼠脊髓半切损害后，hBMSCs组动物较PBS组死亡率下降并有明显的神经功能恢复。移植的hBMSCs 在宿主脊髓中存活，从第7天开始即有NeuN和GFAP表达并向损伤部位及对侧迁移，第28天hBMSCs来源GFAP阳性细胞可见明显的树突生长。结论：hBMSCs可在宿主损伤脊髓中存活、向损伤部位迁移并向神经元和星形胶质细胞分化，并促进神经功能恢复，降低死亡率，成人骨髓间质干细胞作为一种独特的干细胞来源用于治疗脊髓损伤可能具有非常重要的价值。     

Bone marrow mesenchymal stem cells stimulated with low‐intensity pulsed ultrasound: Better choice of transplantation treatment for spinal cord injury

Stem cell transplantation, especially treatment with bone marrow mesenchymal stem cells (BMSCs), has been considered a promising therapy for the locomotor and neurological recovery of spinal cord injury (SCI) patients. However, the clinical benefits of BMSCs transplantation remain limited because of the considerably low viability and inhibitory microenvironment. In our research, low‐intensity pulsed ultrasound (LIPUS), which has been widely applied to clinical applications and fundamental research, was employed to improve the properties of BMSCs. The most suitable intensity of LIPUS stimulation was determined. Furthermore, the optimized BMSCs were transplanted into the epicenter of injured spinal cord in rats, which were randomized into four groups: (a) Sham group (n = 10), rats received laminectomy only and the spinal cord remained intact. (b) Injury group (n = 10), rats with contused spinal cord subjected to the microinjection of PBS solution. (c) BMSCs transplantation group (n = 10), rats with contused spinal cord were injected with BMSCs without any priming. (d) LIPUS‐BMSCs transplantation group (n = 10), BMSCs stimulated with LIPUS were injected at the injured epicenter after contusion. Rats were then subjected to behavioral tests, immunohistochemistry, and histological observation. It was found that BMSCs stimulated with LIPUS obtained higher cell viability, migration, and neurotrophic factors expression in vitro. The rate of apoptosis remained constant. After transplantation of BMSCs and LIPUS‐BMSCs postinjury, locomotor function was significantly improved in LIPUS‐BMSCs transplantation group with higher level of brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the epicenter, and the expression of neurotrophic receptor was also enhanced. Histological observation demonstrated reduced cavity formation in LIPUS‐BMSCs transplantation group when comparing with other groups. The results suggested LIPUS can improve BMSCs viability and neurotrophic factors expression in vitro, and transplantation of LIPUS‐BMSCs could promote better functional recovery, indicating possible clinical application for the treatment of SCI.     

Human umbilical cord blood stem cell transplantation for the treatment of chronic spinal cord injury Electrophysiological changes and long-term efficacy

Stem cell transplantation can promote functional restoration following acute spinal cord injury (injury time < 3 months), but the safety and long-term efficacy of this treatment need further exploration. In this study, 25 patients with traumatic spinal cord injury (injury time > 6 months) were treated with human umbilical cord blood stem cells via intravenous and intrathecal injection. The follow-up period was 12 months after transplantation. Results found that autonomic nerve functions were restored and the latent period of somatosensory evoked potentials was reduced. There were no severe adverse reactions in patients following stem cell transplantation. These experimental findings suggest that the transplantation of human umbilical cord blood stem cells is a safe and effective treatment for patients with traumatic spinal cord injury.     

局部注射骨髓间充质干细胞治疗大鼠脊髓损伤：运动功能有改善吗？

背景：目前研究多为骨髓间充质干细胞的体外培养及细胞移植对颅内疾病的治疗,对植入细胞在损伤脊髓中的成活、分化、迁移、结构重建等了解有限。 目的：探讨局部骨髓间充质干细胞移植在脊髓损伤修复中的作用和骨髓间充质干细胞替代治疗的可行性。 方法：成年健康雌性SD大鼠随机分为细胞移植组和对照组,建立SD大鼠脊髓横断损伤模型,伤后即刻分别向损伤区局部移植大鼠骨髓间充质干细胞悬液或无钙镁磷酸缓冲液。在术前和术后1 d,1周,2周,3周,4周和8周进行BBB评分,观测大鼠的运动功能,并于移植后1周免疫组织化学染色法观察BrdU标记的骨髓间充质干细胞在脊髓损伤处的存活情况,移植后4周进行损伤脊髓的大体观察和组织学检测。 结果与结论：移植后第1~8周细胞移植组BBB评分均髙于对照组;术后1周免疫组织化学染色结果显示在细胞移植组大鼠脊髓远端检测到BrdU阳性细胞,术后4周脊髓损伤处发现有神经纤维。证实通过损伤后立即局部注射的方式将骨髓间充质干细胞移植进大鼠脊髓损伤区,细胞可在损伤区存活;存活的骨髓间充质干细胞可分化为神经元,在损伤局部形成神经元通路,从而促进脊髓神经纤维传导功能的恢复,并促进高位脊髓损伤后大鼠后肢运动功能恢复。     

BDNF-GFP转染神经干细胞修复大鼠脊髓损伤：发挥干细胞与神经因子的双重效应？

摘要 背景：神经干细胞移植入大鼠脊髓损伤模型可以促进功能恢复,基因治疗已被广泛用于治疗脊髓损伤。 目的：确定BDNF-GFP转染后神经干细胞移植对大鼠脊髓损伤的修复效果。 设计,时间和背景：本实验是在中国医科大学基础医学院发育生物学实验室与2009年5月至2010年1月完成。 材料：10只新生Wistar大鼠和88只2-3个月大,雌雄不限的Wistar大鼠。 方法：以携带BDNF-GFP基因的腺病毒转染神经干细胞。88只Wistar大鼠中假手术组8只, 80只大鼠制成T9左侧横断模型,并随机分成四组：BDNF和GFP修饰的神经干细胞移植组,GFP修饰的神经干细胞移植组;单纯神经干细胞移植组和模型组。在各神经干细胞移植组,脊髓损伤后向横断处显微注射等体积细胞,模型组在相同的部位注射等体积的PBS。 主要观察指标： BBB评分检测脊髓损伤模型运动功能恢复情况;制备脊髓损伤模型2周后取材,免疫组化评估BDNF-GFP转染的神经干细胞移植后的细胞学特点;制备脊髓损伤模型2、4、6、8周Real-time PCR检测脊髓横断处BDNF表达情况。 结果： BDNF-GFP转染后神经干细胞在脊髓半切模型中存活并表达BDNF和GFP,移植该细胞后的大鼠体内高表达具有生物活性的BDNF,且脊髓损伤动物运动功能较对照组明显恢复。 结论：移植BDNF-GFP转染后神经干细胞可能是一种修复脊髓损伤的有效的方法。 关键词：神经干细胞,脑源性神经营养因子;绿色荧光蛋白;脊髓损伤;移植。     

Combined NgR vaccination and neural stem cell transplantation promote functional recovery after spinal cord injury in adult rats

C‐J. Xu, L. Xu, L‐D. Huang, Y. Li, P‐P. Yu, Q. Hang, X‐M. Xu and P‐H. Lu (2011) Neuropathology and Applied Neurobiology 37, 135–155
Combined NgR vaccination and neural stem cell transplantation promote functional recovery after spinal cord injury in adult rats Aims: After spinal cord injury (SCI), there are many adverse factors at the lesion site such as glial scar, myelin‐derived inhibitors, cell loss and deficiency of neurotrophins that impair axonal regeneration. Therefore, combination therapeutic strategies might be more effective than a single strategy for promoting functional recovery after SCI. In the present study, we investigated whether a Nogo66 receptor (NgR) vaccine, combined with neural stem cell (NSC) transplantation, could promote better functional recovery than when NgR vaccine or NSCs were used alone. Methods: Adult rats were immunized with NgR vaccine at 1 week after a contusive SCI at the thoracic level, and the NSCs, obtained from green fluorescent protein transgenic rats, were transplanted into the injury site at 8 weeks post injury. The functional recovery of the animals under various treatments was evaluated by three independent behavioural tests, that is, Basso, Beattie and Bresnahan locomotor rating scale, footprint analysis and grid walking. Results: The combined therapy with NgR vaccination and NSC transplantation protected more ventral horn motor neurones in the injured spinal cord and greater functional recovery than when they were used alone. Furthermore, NgR vaccination promoted migration of engrafted NSCs along the rostral‐caudal axis of the injured spinal cords, and induced their differentiation into neurones and oligodendrocytes in vivo. Conclusions: The combination therapy of NgR vaccine and NSC transplantation exhibited significant advantages over any single therapy alone in this study. It may represent a potential new therapy for SCI.     

Points regarding cell transplantation for the treatment of spinal cord injur y

Transplantation of somatic cells, including bone marrow stromal cells (BMSCs), bone marrow mononu-clear cells (BMNCs), and choroid plexus epithelial cells (CPECs), enhances the outgrowth of regenerating axons and promotes locomotor improvements. They are not integrated into the host spinal cord, but disappear within 2-3 weeks after transplantation. Regenerating axons extend at the spinal cord lesion through the astrocyte-devoid area that is iflled with connective tissue matrices. Regenerating axons have characteristics of peripheral nerves:they are associated with Schwann cells, and embedded in connective tissue matrices. It has been suggested that neurotrophic factors secreted from BMSCs and CPECs promote“intrinsic”ability of the spinal cord to regenerate. Transplanted Schwann cells survive long-term, and are integrated into the host spinal cord, serving as an effective scaffold for the outgrowth of regenerating axons in the spinal cord. The disadvantage that axons are blocked to extend through the glial scar at the border of the lesion is overcome. Schwann cells have been approved for clinical applications. Neural stem/progenitor cells (NSPCs) survive long-term, proliferate, and differentiate into glial cells and/or neurons after trans-plantation. No method is available at present to manipulate and control the behaviors of NPSCs to allow them to appropriately integrate into the host spinal cord. NPSP transplantation is not necessarily effective for locomotor improvement.     

神经干细胞移植促进鼠脊髓损伤后髓鞘结构的修复

目的 观察神经干细胞移植治疗对鼠脊髓损伤后髓鞘结构修复的作用并探讨其作用机制。方法 制备鼠T10脊髓损伤模型,体外培养、诱导鼠神经干细胞,定量评价神经干细胞移植对脊髓损伤后髓鞘结构修复的影响。结果 与对照组相比,神经干细胞移植组明显地增强了蛋白前脂蛋白信使核糖核酸(PLP mRNA)的表达,促进了髓鞘碱性蛋白(MBP)性的髓鞘再生和髓鞘结构的修复。结论 神经干细胞移植通过增强髓鞘的再生而促进了脊髓损伤后髓鞘结构的修复,是急性脊髓损伤一种有效的治疗方案。