Stem cell-based cell therapy for spinal cord injury

Traumatic injuries to the spinal cord lead to severe and permanent neurological deficits. Although no effective therapeutic option is currently available, recent animal studies have shown that cellular transplantation strategies hold promise to enhance functional recovery after spinal cord injury (SCI). This review is to analyze the experiments where transplantation of stem/progenitor cells produced successful functional outcome in animal models of SCI. There is no consensus yet on what kind of stem/progenitor cells is an ideal source for cellular grafts. Three kinds of stem/progenitor cells have been utilized in cell therapy in animal models of SCI: embryonic stem cells, bone marrow mesenchymal stem cells, and neural stem cells. Neural stem cells or fate-restricted neuronal or glial progenitor cells were preferably used because they have clear capacity to become neurons or glial cells after transplantation into the injured spinal cord. At least a part of functional deficits after SCI is attributable to chronic progressive demyelination. Therefore, several studies transplanted glial-restricted progenitors or oligodendrocyte precursors to target the demyelination process. Directed differentiation of stem/progenitor cells to oligodendrocyte lineage prior to transplantation or modulation of microenvironment in the injured spinal cord to promote oligodendroglial differentiation seems to be an effective strategy to increase the extent of remyelination. Transplanted stem/progenitor cells can also contribute to promoting axonal regeneration by functioning as cellular scaffolds for growing axons. Combinatorial approaches using polymer scaffolds to fill the lesion cavity or introducing regeneration-promoting genes will greatly increase the efficacy of cellular transplantation strategies for SCI.     

Traumatic axonal injury in the spinal cord evoked by traumatic brain injury

Although it is well known that traumatic brain injury (TBI) evokes traumatic axonal injury (TAI) within the brain, TBI-induced axonal damage in the spinal cord (SC) has been less extensively investigated. Detection of such axonal injury in the spinal cord would further the complexity of TBI while also challenging some functional neurobehavioral endpoints frequently used to assess recovery in various models of TBI. To assess TAI in the spinal cord associated with TBI, we analyzed the craniocervical junction (CCJ), cervico-thoracic (CT), and thoraco-lumber (ThL) spinal cord in a rodent model of impact acceleration of TBI of varying severities. Rats were transcardially fixed with aldehydes at 2, 6, and 24 h post-injury (n = 36); each group included on sham-injured rodent. Semi-serial vibratome sections were reacted with antibodies targeting TAI via alteration in cytoskeletal integrity or impaired axonal transport. Consistent with previous observations in this model, the CCJ contained numerous injured axons. Immunoreactive, damaged axonal profiles were also detected as caudal, as the ThL spinal cord displayed morphological characteristics entirely consistent with those described in the brainstem and the CCJ. Quantitative analyses demonstrated that the occurrence and extent of TAI is positively associated with the impact/energy of injury and negatively with the distance from the brainstem. These observations show that TBI can evoke TAI in regions remote from the injury site, including the spinal cord itself. This finding is relevant to shaken baby syndrome as well as during the analysis of data in functional recovery in various models of TBI.     

Axonal remyelination by cord blood stem cells after spinal cord injury

Human umbilical cord blood stem cells (hUCB) hold great promise for therapeutic repair after spinal cord injury (SCI). Here, we present our preliminary investigations on axonal remyelination of injured spinal cord by transplanted hUCB. Adult male rats were subjected to moderate SCI using NYU Impactor, and hUCB were grafted into the site of injury one week after SCI. Immunohistochemical data provides evidence of differentiation of hUCB into several neural phenotypes including neurons, oligodendrocytes and astrocytes. Ultrastructural analysis of axons reveals that hUCB form morphologically normal appearing myelin sheaths around axons in the injured areas of spinal cord. Colocalization studies prove that oligodendrocytes derived from hUCB secrete neurotrophic hormones neurotrophin-3 (NT3) and brain-derived neurotrophic factor (BDNF). Cord blood stem cells aid in the synthesis of myelin basic protein (MBP) and proteolipid protein (PLP) of myelin in the injured areas, thereby facilitating the process of remyelination. Elevated levels of mRNA expression were observed for NT3, BDNF, MBP and PLP in hUCB-treated rats as revealed by fluorescent in situ hybridization (FISH) analysis. Recovery of hind limb locomotor function was also significantly enhanced in the hUCB-treated rats based on Basso-Beattie-Bresnahan (BBB) scores assessed 14 days after transplantation. These findings demonstrate that hUCB, when transplanted into the spinal cord 7 days after weight-drop injury, survive for at least 2 weeks, differentiate into oligodendrocytes and neurons, and enable improved locomotor function. Therefore, hUCB facilitate functional recovery after moderate SCI and may prove to be a useful therapeutic strategy to repair the injured spinal cord.     

Present situation and future aspects of spinal cord regeneration

The central nervous system (CNS) has a limited capacity for regeneration after injury. In spinal cord injury (SCI) patients, total loss of all motor and sensory function occurs below the level of injury. Advances in treatment are expected for orthopedic and spinal surgeons. Recently, evidence of axonal regeneration and functional recovery has been reported in animal spinal cord injury models. Our studies on the roles of inhibitory molecules with a comparison between neonatal and adult animals may help serve as therapeutic targets to enhance axonal regeneration for the injured spinal cord. Also, our cell replacement study indicates the possibility of transplanting neural stem cells to supply the cell source for immature oligodendrocytes, which are thought to be essential for both the myelination and trophic support of regenerating axons in the spinal cord. Administration of neurotrophic factors, prevention of inhibitory factors, and stem cell technology have clinical applications in SCI patients. However, spinal cord regeneration involves a multistep process, and several factors have to be controlled after injury. A combination of several treatments could overcome a nonpermissive environment for spinal cord regeneration. Further understanding of the mechanisms and finding optimal targets of spinal cord regeneration are necessary to obtain successful therapies for SCI patients.Presented at the 76th Annual Meeting of the Japanese Orthopaedic Association, Kanazawa, Japan, May 23, 2003     

Stem cell transplantation and other novel techniques for promoting recovery from spinal cord injury

A number of potential approaches aim to optimize functional recovery after spinal cord injury. They include minimizing the progression of secondary injury, manipulating the neuroinhibitory environment of the spinal cord, replacing lost tissue with transplanted cells or peripheral nerve grafts, remyelinating denuded axons, and maximizing the intrinsic regenerative potential of endogenous progenitor cells. We review the application of stem cell transplantation to the spinal cord, emphasizing the use of embryonic stem cells for remyelinating damaged axons. We speculate that harnessing the potential of endogenously born stem cells already present in the spinal cord represents an important therapeutic target. We also discuss the potential application of peripheral nervous system reconstruction to recovery from spinal cord injury. The principles of peripheral nerve regeneration and concepts of nerve grafting are reviewed. Particular attention is given to peripheral nerve allotransplantation for repairing extensively injured tissue when autologous donor nerve material is scarce. The potential role of nerve transfers for reconstructing the injured spinal cord, particularly the cauda equina and lumbosacral plexus, are also described.     

Effect of fetal spinal cord graft with different methods on axonal pathology after spinal cord contusion

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手术减压时间对损伤脊髓轴索病理和损伤区面积的影响

目的 探讨大鼠脊髓损伤后手术减压时间对大鼠脊髓轴索病理和损伤区面积的影响。方法 将动物分为两组：大鼠脊髓挫伤2h手术减压组（A组），大鼠脊髓挫伤8h手术减压组（B组）。手术后1、3、7、14、28d进行轴索病理变化的观察并测量脊髓损伤面积，采用计算机图像分析技术，进行定量分析。计算Tarlv评分并检测感觉诱发电位（SEP）和运动诱发电位（MEP）。结果 图象分析发现：脊髓损伤后B组轴索丢失明显多于A组。脊髓损伤面积B组亦明显大于A组；大鼠后肢功能Tarlv评分和电生理检查也有类似的变化趋势。结论 大鼠脊髓损伤后早期手术减压对损伤的大鼠脊髓轴索有保护作用，能减少脊髓损伤面积，并促进大鼠后肢功能恢复。     

Schwann cell transplantation for repair of the adult spinal cord

The Schwann cell is one of the most widely studied cell types for repair of the spinal cord. These cells play a crucial role in endogenous repair of peripheral nerves due to their ability to dedifferentiate, migrate, proliferate, express growth promoting factors, and myelinate regenerating axons. Following trauma to the spinal cord, Schwann cells migrate from the periphery into the injury site, where they apparently participate in endogenous repair processes. For transplantation into the spinal cord, large numbers of Schwann cells are necessary to fill injury-induced cystic cavities. Several culture systems have been developed that provide large, highly purified populations of Schwann cells. Importantly, the development of in vitro systems to harvest human Schwann cells presents a unique opportunity for autologous transplantation in the clinic. In animal models of spinal cord injury (SCI), grafting Schwann cells or peripheral nerve into the lesion site has been shown to promote axonal regeneration and myelination. However, axons do not regenerate beyond the transplant due to the inhibitory nature of the glial scar surrounding the injury. To overcome the glial scar inhibition, additional approaches such as increasing the intrinsic capacity of axons to regenerate and/or removal of the inhibitory molecules associated with reactive astrocytes and/or oligodendrocyte myelin should be incorporated. Clearly, Schwann cells have great potential for repair of the injured spinal cord, but they need to be combined with other interventions to maximize axonal regeneration and functional recovery.     

Transplantation of oligodendrocyte precursor cells improves myelination and promotes functional recovery after spinal cord injury

Loss of oligodendrocytes and demyelination further impair neural function after spinal cord injury (SCI). Replacement of lost oligodendrocytes and improvement of myelination have a therapeutic significance in treatment of SCI. Here, we transplanted oligodendrocyte precursor cells (OPCs) to improve myelination in a rat model of contusive SCI. The labelled OPCs were transplanted to injured cord 7 days after injury. As a result, the implanted cells still survived in vivo 8 weeks after transplantation. They proliferated, integrated and differentiated in the injured cord. In the OPCs-treated rats, enhanced myelination in the lesioned area was observed and substantial improvement of motor function and nerve conduction was also recorded. Thus, this study provides strong evidence to support that transplantation of OPCs could improve myelination of injured cord and enhance functional recovery after contusive SCI.     

Cellular transplantation and spinal cord injury

Spinal cord injury is often characterized by immediate and irreversible loss of sensory and motor functions below the level of injury. Cellular transplantation in various experimental models of spinal cord injury has been used as a strategy for reducing deficits and improving functional recovery. The general strategy has been aimed at promoting regeneration of intrinsic injured axons with the development of alternative pathways that facilitate a partial functional connection. Other objectives of cellular transplantation studies have included replacement of lost cellular elements, alleviation of chronic pain, and modulation of the inflammatory response after injury. This review focuses on the cell types that have been used in spinal cord transplantation studies in the context of evolving biological perspectives, technological advances, and new therapeutic strategies and serves as a point of reference for future studies.     

Lithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury

After spinal cord injury, enzymatic digestion of chondroitin sulfate proteoglycans promotes axonal regeneration of central nervous system neurons across the lesion scar. We examined whether chondroitinase ABC (ChABC) promotes the axonal regeneration of rubrospinal tract (RST) neurons following injury to the spinal cord. The effect of a GSK-3beta inhibitor, lithium chloride (LiCl), on the regeneration of axotomized RST neurons was also assessed. Adult rats received a unilateral hemisection at the seventh cervical spinal cord segment (C7). Four weeks after different treatments, regeneration of RST axons across the lesion scar was examined by injection of Fluoro-Gold at spinal segment T2, and locomotor recovery was studied by a test of forelimb usage. Injured RST axons did not regenerate spontaneously after spinal cord injury, and intraperitoneal injection of LiCl alone did not promote the regeneration of RST axons. Administration of ChABC at the lesion site enhanced the regeneration of RST axons by 20%. Combined treatment of LiCl together with ChABC significantly increased the regeneration of RST axons to 42%. Animals receiving combined treatment used both forelimbs together more often than animals that received sham or single treatment. Immunoblotting and immunohistochemical analysis revealed that LiCl induced the expression of inactive GSK-3beta as well as the upregulation of Bcl-2 in injured RST neurons. These results indicate that in vivo, LiCl inhibits GSK-3beta and reinforces the regeneration-promoting function of ChABC through a Bcl-2-dependent mechanism. Combined use of LiCl together with ChABC could be a novel treatment for spinal cord injury.     

Origin of regenerated axons in nerve bypass grafts

It has been shown that end-to-side coaptation and nerve bypass grafting, which are essentially two sequential end-to-side coaptations, induce axonal outgrowth in peripheral nerve injuries. However, it is unknown whether the axons regenerated after end-to-side coaptation originate by collateral sprouting at the suture site or by elongation from the spinal neuronal pool. Also unknown is the extent of functional recovery that can be expected after bypass grafting for the reconstruction of injured peripheral nerves. We conducted a study to evaluate the origin of regenerated axons after end-to-side coaptation and the utility of nerve bypass grafting for peripheral nerve injury. For this purpose, we performed electrophysiological studies using bypass grafting (end-to-side coaptation) and conventional cable grafting (end-to-end coaptation) to treat complete paralysis of the peroneal nerve in rabbit models, and compared the recovery time and extent of functional recovery achieved with the two techniques. We assessed, by electromyography, the time to appearance of reinnervation potentials from the tibialis anterior muscle on the affected side. These times were not significantly different in the two study groups of animals (p = 0.5390). After a 12-week recovery period, electrophysiological findings and histological assessment showed similar recovery in both groups of animals. It is known that collateral sprouting of axons from the nodes of Ranvier proximal to the transected nerve stump occurs in cable grafting, and that axon elongation from the spinal cord requires more time. Our findings in the present study strongly suggest that collateral sprouting across end-to-side sutures is the chief means of axonal outgrowth in nerve bypass grafts, and that functional recovery can be expected in bypass grafting to nearly the same extent as in cable grafting.     

GDNF基因修饰的嗅鞘细胞移植联合IN-1注射修复大鼠急性脊髓损伤

目的 研究胶质细胞源性神经营养因子(GDNF)基因修饰的嗅鞘细胞(OECs)移植联合轴突生长抑制蛋白抗体(IN-1)局部持续注射对大鼠急性横断性脊髓损伤(SCI)的修复作用.方法 构建载有GDNF基因的慢病毒(Lentivirus)载体并体外转染OECs,Western Blot检测GDNF的表达.用50只成年雌性SD大鼠建立胸脊髓全横断损伤模型,随机分为A(对照组)、B(IN-1微泵注射组)、C(OECs组)、D(GDNF-OECs组)和E(GDNF-OECs+IN-1组)5组各10只.应用神经丝蛋白200(NF200)单抗免疫组化、生物素化的葡聚糖胺(BDA),顺行神经追踪对SCI区神经纤维再生进行形态学观察.采用BBB评分评估大鼠后肢功能恢复情况.结果 术后共有13只大鼠死亡.术后8周可观察到Hoechst标记的OECs在体内存活并在脊髓内迁移;E组和D组可见SCI区杂乱无序的再生轴突,有连续性神经纤维通过损伤区;C组可见少量无序的再生轴突,可疑连续性神经纤维通过损伤区;B组和A组脊髓残端萎缩,未见轴突再生.A、B、C、D和E组后肢功能运动平均BBB评分分别为7.70±0.24、7.89±0.15、10.50±0.25、11.43±0.23和12.81±0.40.结论 GDNF-OECs移植联合IN-1抗体注射可有效促进损伤脊髓神经轴突的存活、再生,促进损伤脊髓的修复.     

Functional assessment of the acute local and distal transplantation of human neural stem cells after spinal cord injury

Background context

Spinal cord injury can lead to severe functional impairments secondary to axonal damage, neuronal loss, and demyelination. The injured spinal cord has limited regrowth of damaged axons. Treatment remains controversial, given inconsistent functional improvement. Previous studies demonstrated functional recovery of rats with spinal cord contusion after transplantation of rat fetal neural stem cells.

Purpose

We hypothesized that acute transplantation of human fetal neural stem cells (hNSCs) both locally at the injury site as well as distally via intrathecal injection would lead to improved functional recovery compared with controls.

Study design/setting

Twenty-four adult female Long-Evans hooded rats were randomized into four groups with six animals in each group: two experimental and two control. Functional assessment was measured after injury and then weekly for 6 weeks using the Basso, Beattie, and Bresnahan Locomotor Rating Score. Data were analyzed using two-sample t test and linear mixed-effects model analysis.

Methods

Posterior exposure and laminectomy at T10 level was used. Moderate spinal cord contusion was induced by the Multicenter Animal Spinal Cord Injury Study Impactor with 10-g weight dropped from a height of 25 mm. Experimental subjects received either a subdural injection of hNSCs locally at the injury site or intrathecal injection of hNSCs through a separate distal laminotomy. Controls received control media injection either locally or distally.

Results

Statistically significant functional improvement was observed in local or distal hNSCs subjects versus controls (p=.034 and 0.016, respectively). No significant difference was seen between local or distal hNSC subjects (p=.66).

Conclusions

Acute local and distal transplantation of hNSCs into the contused spinal cord led to significant functional recovery in the rat model. No statistical difference was found between the two techniques.     

Experimental bypass surgery between the spinal cord and caudal nerve roots for spinal cord injuries

Spinal cord injuries often cause permanent neurological deficits and are still considered as inaccessible to efficient therapy. Injured spinal cord axons are unable to spontaneously regenerate in adult mammalians. Re-establishing functional activity especially in the lower limbs by reinnervating the caudal infra-lesional territories could represent an attractive therapeutic strategy. For several years, we have studied and developed surgical bypasses using peripheral nerve grafts bridging the supra-lesional rostral spinal cord to the caudal infra-lesional lumbar roots. Main objectives were: 1- to overcome the spinal cord lesion and the consecutive glial barrier blocking the axonal regeneration; 2- to find and bring an alternative source of regenerating axons; 3- to guide those axons toward precisely definite targets (for example, lower limb muscles). We report here the results of our experimental research, which led us from animal experimental models (rodents, primates) to the first human experimentation. Limitations of the method (especially technical pitfalls) are numerous. However, we have obtained encouraging results in our attempts to "repair" the motor pathway. Functional recovery with strong evidence of centrifugal axonal regeneration from the spinal cord to the periphery has been observed. Regarding the sensory pathway, we have found evidence of centripetal axonal regeneration from the periphery toward the spinal cord. Further studies are obviously advocated, but our experimental model of spinal cord - nerve roots bypasses may be integrated in future "repair" strategies of both motor and sensory pathways following spinal cord injury.     

Antibodies neutralizing Nogo-A increase pan-cadherin expression and motor recovery following spinal cord injury in rats

STUDY DESIGN: A rat model of spinal cord injury was used to test the hypothesis that Nogo-A monoclonal antibody (NEP1-40) promotes morphologic and functional recoveries of injured spinal cord. OBJECTIVE: Nogo-A is a myelin-associated neurite outgrowth inhibitory protein, which blocks elongation nerve fibers and limits neuronal regeneration after central nervous system injury. METHODS: Forty-four rats were utilized and allocated into control (vehicle) and NEP1-40-treated groups. In all animals, the spinal cord was hemi-transected at Th-10 and phosphate-buffered saline solution was immediately applied on the injured area in the control group. NEP1-40 solution was immediately applied on the hemi-transected area in the treatment group. Each group was subdivided into three subgroups according to the postsurgical day of killing (3, 8 and 21 days). The spinal cords were removed for analysis. RESULTS: Motor scores in the NEP1-40-treated groups were significantly higher than those in the vehicle groups both at 8 and 21 days post injury. Immunohistochemical staining for pan-cadherin, a marker of neuronal cell adhesion and axonal sprouting, revealed a significant increase in staining in the NEP1-40 treatment group at 8 and 21 days post injury. Transmission electron microscopical evaluation revealed degeneration of the myelin and loss of cytoarchitectural organization in the axons of controls. Better preservation and normal histologic features were observed in the NEP1-40-treated groups. CONCLUSION: We have demonstrated improved preservation of injured axons and significant pan-cadherin expression after NEP1-40 treatment after the spinal cord injury. Inhibition of Nogo-A may improve the capacity for neuronal regeneration after spinal cord injury.     

Dissociated predegenerated peripheral nerve transplants for spinal cord injury repair: a comprehensive assessment of their effects on regeneration and functional recovery compared to schwann cell transplants

Abstract Several recent studies suggest that predegenerated nerves (PDNs) or dissociated PDNs (dPDNs) can improve behavioral and histological outcomes following transplantation into the injured rat spinal cord. In the current study we tested the efficacy of dPDN transplantation by grafting cells isolated from the sciatic nerve 7 days after crush. We did not replicate one study, but rather assessed what appeared, based on five published reports, to be a reported robust effect of dPDN grafts on corticospinal tract (CST) regeneration and locomotor recovery. Using a standardized rodent spinal cord injury model (200 kD IH contusion) and transplantation procedure (injection of GFP(+) cells 7 days post-SCI), we demonstrate that dPDN grafts survive within the injured spinal cord and promote the ingrowth of axons to a similar extent as purified Schwann cell (SC) grafts. We also demonstrate for the first time that while both dPDN and SC grafts promote the ingrowth of CGRP axons, neither graft results in mechanical or thermal hyperalgesia. Unlike previous studies, dPDN grafts did not promote long-distance axonal growth of CST axons, brainstem spinal axons, or ascending dorsal column sensory axons. Moreover, using a battery of locomotor tests (Basso Beattie Bresnahan [BBB] score, BBB subscore, inked footprint, Catwalk, and ladderwalk), we failed to detect any beneficial effects of dPDN transplantation on the recovery of locomotor function after SCI. We conclude that dPDN transplants are not sufficient to promote CST regeneration or locomotor recovery after SCI.     

Biodegradable polymer grafts for surgical repair of the injured spinal cord

PURPOSE: Biodegradable polymers have been used in the surgical repair of peripheral nerves, but their potential for use in the central nervous system has not been exploited adequately. This article discusses concepts related to the engineering of a biodegradable polymer graft for surgical repair of the injured spinal cord and explores the potential means by which such a device might promote axon regeneration and functional recovery after spinal cord injury. CONCEPT: A biodegradable polymer implant with controlled microarchitecture can be engineered, and its composition can be optimized for implantation in the spinal cord. RATIONALE: The use of a biodegradable polymer implant has the dual advantages of providing a structural scaffold for axon growth and a conduit for sustained-release delivery of therapeutic agents. As a scaffold, the microarchitecture of the implant can be engineered for optimal axon growth and transplantation of permissive cell types. As a conduit for the delivery of therapeutic agents that may promote axon regeneration, the biodegradable polymer offers an elegant solution to the problems of local delivery and controlled release over time. Thus, a biodegradable polymer graft would theoretically provide an optimal structural, cellular, and molecular framework for the regrowth of axons across a spinal cord lesion and, ultimately, neurological recovery. CONCLUSION: Biodegradable polymer grafts may have significant therapeutic potential in the surgical repair of the injured spinal cord. Further research should be focused on the bioengineering, characterization, and experimental application of these devices.     

Autopsy verifies demyelination and lack of vascular damage in partially reversible radiation myelopathy

STUDY DESIGN: Case report of recovering radiation myelopathy. OBJECTIVE: To present autopsy and functional imaging findings on a unique case of slowly recovering radiation myelopathy with the aim of the clarification of the underlying mechanism. PATIENT: The cervical spinal cord and the distal part of the medulla oblongata of a 36-year-old thyroid cancer patient had been incorrectly irradiated with a total dose of 61 Gy and a fraction size of 3.4 Gy (J Neurol Sci 1999; 163:39-43), resulting in incomplete cervical transection with a 5-month latency period following the termination of radiotherapy. This was followed by a 9.5-year spontaneous improvement until her demise, during which the check-ups were supplemented by positron emission tomography (PET) investigations; these indicated increased [18F]deoxyglucose and [15O]butanol uptakes, but a diminished [11C]methionine accumulation by the irradiated spinal cord segment. RESULTS: Autopsy revealed demyelination (with axonal loss) and neuronal damage in the cervical spinal cord and the distal part of the medulla oblongata. In the same region, only minimal vascular injury (thickening of some of the capillary walls) was detected, but not cell proliferation or chronic inflammation. Bilateral, secondary pyramidal tract degeneration caudal to the irradiated segment was observed. The PET and autopsy findings, although separated by 2 years, are consistent. CONCLUSIONS: The pathological state of the spinal cord revealed by the autopsy is concordant with the incomplete cervical transection, implying that the functional recovery is supported by a process that probably differs from the restoration of the mechanism destroyed by the radiotherapy. For the restoration of the function, we suggest an altered conduction mechanism of the action potential, involving an increased number of sodium channels along the demyelinated segments of the injured axons, which is fully congruent with the PET findings.     

神经营养素-3基因修饰嗅鞘细胞移植对急性脊髓损伤作用的实验研究

目的：观察神经营养素-3（NT-3）基因转染嗅鞘细胞（OEG）移植对急性大鼠脊髓损伤的作用。方法：将自行构建的质粒DEGFP-NT3应用脂质体介导的方法导人体外培养的嗅鞘细胞，并移植入急性脊髓损伤大鼠体内．连续观察12周．与接受单纯OEG、空白质粒转染OEG移植的脊髓损伤大鼠进行比较。结果：移植转染DEGFP-NT3后的OEG能在体内长期存活，表达NT-3基因，与对照组比较能更好地促进脊髓损伤区轴突的再生和后肢功能的恢复。结论：OEG是脊髓损伤基因治疗较好的受体细胞。转染NT-3基因的OEG移植后可以在体内较长时间存活．能明显促进急性脊髓损伤神经纤维的再生和功能恢复，为基因修饰嗅鞘细胞在脊髓损伤治疗中的应用提供了实验和理论依据。