Wnt1 and Wnt2b immunodetection of the regenerating tail and comparative ultrastructure of tail spinal cord in the Scincella tsinlingensis / Inmunodetección Wnt1 y Wnt2b de la cola en regeneración y ultraestructura comparativa de la médula espinal de la cola en Scincella tsinlingensis

SUMMARY: The Wnt pathway is essential for the initiation of lizard tail regeneration. The regenerated lizard tails exhibit obvious morphological differences compared to the original ones. The expression of Wnt1 and Wnt2b proteins in the regenerating tail of Scincella tsinlingensis was detected by immunohistochemistry and then comparatively analyzed for ultrastructural changes in the original and regenerated spinal cord. The ependymal layer of the original spinal cord was pseudostratified with multiciliated cells and primary monociliated cells, while the cells of the ependymal layer of the regenerated spinal cord were organized in a monolayer with a few biciliated cells. Immunolocalization indicated that Wnt1 and Wnt2b were mainly distributed in the dermis near the original tail stump, spinal cord, and clot-positive migratory cells during Stage I, 0-1 days post-amputation (dpa). Wnt1 and Wnt2b were predominantly detected in the epaxial and hypaxial musculature near the original tail stump, wound epithelium, and spinal cord in the original tail during Stage II, 1-7 dpa. Mesenchymal cells and wound epithelium showed immunostaining during Stage III and IV, 7-15 dpa. The ependymal tubes contained these signaling proteins during Stage V and VI, 20- 30 dpa. Labeling was mainly observed in nearby regenerative blood vessels, ependymal cells, epaxial and hypaxial musculature in the apical epithelial layer (AEC) after 45-160 dpa. These findings indicated that Wnt1 and Wnt2b proteins presented primarily in regenerating epidermis and nerve tissues were a critical signal for tail regeneration in S. tsinlingensis.

RESUMEN: La vía Wnt es esencial para el inicio de la regeneración de la cola del lagarto. Las colas de lagarto regeneradas exhiben diferencias morfológicas obvias en comparación con las originales. La expresión de las proteínas Wnt1 y Wnt2b en la cola en regeneración de Scincella tsinlingensis se detectó mediante inmunohistoquímica y luego se analizaron comparativamente los cambios ultraestructurales en la médula espinal original y regenerada. La capa ependimaria de la médula espinal original se pseudoestratificó con células multiciliadas y células monociliadas primarias, mientras que las células de la capa ependimaria de la médula espinal regenerada se organizaron en monocapa con algunas células bicilicadas. La inmunolocalización indicó que Wnt1 y Wnt2b se distribuyeron principalmente en la dermis cerca del muñón de la cola original, la médula espinal y las células migratorias positivas en el coágulo durante la Etapa I, 0-1 días después de la amputación (dpa). Wnt1 y Wnt2b se detectaron predominantemente en la musculatura epaxial e hipaxial cerca del muñón de la cola original, el epitelio de la herida y la médula espinal en la cola original durante la Etapa II, 1-7 dpa. Las células mesenquimales y el epitelio de la herida mostraron inmunomarcaje durante la Etapa III y IV, 7- 15 dpa. Los tubos ependimarios contenían estas proteínas de señalización durante la Etapa V y VI, 20-30 dpa. El marcaje se observó principalmente en vasos sanguíneos regenerativos cercanos, células ependimarias, musculatura epaxial e hipaxial en la capa epitelial apical (AEC) después de 45-160 dpa. Estos hallazgos indicaron que las proteínas Wnt1 y Wnt2b están presentes principalmente en la epidermis en regeneración y en los tejidos nerviosos y eran una señal crítica para la regeneración de la cola en S. tsinlingensis.

The efficacy of immediate implantation of macroporous poly(N-[2-hydroxypropyl]-methacrylamide) hydrogel after laceration spinal cord injury in young rats / Eficacia de la implantación inmediata de hidrogel macroporoso de poli (N- [2-hidroxipropil] - metacrilamida) después de una lesión de la médula espinal en ratas jóvenes

SUMMARY: Spinal cord regeneration after mechanical injury is one of the most difficult biomedical problems. This article evaluates the effect of poly(N-[2-hydroxypropyl]-methacrylamide) hydrogel (PHPMA-hydrogel) on spinal cord regeneration in young rats after lateral spinal cord hemi-excision (laceration) at the level of segments T12-T13 (TrGel group). The locomotor function score (FS) and the paretic hindlimb spasticity score (SS) were assessed according to Basso-Beattie-Bresnahan (BBB) and Ashworth scales, respectively, and compared to a group of animals with no matrix implanted (Tr group). Regeneration of nerve fibers at the level of injury was evaluated at ~5 months after spinal cord injury (SCI). One week after the SCI induction, the FS on the BBB scale was 0.9±0.5 points in the Tr group and 3.6±1.2 points in the TrGel group. In the Tr group, the FS in 5 months was significantly lower than in 2 weeks after SCI, while no significant changes in FS were detected in the TrGel group over the entire observation period. The final FS was 0.8±0.3 points in the Tr group and 4.5±1.8 points in the TrGel group. No significant changes in SS have been observed in the TrGel group throughout the experiment, while the Tr group showed significant increases in SS at 2nd week, 6th week, 3th month and 5th month. The SS in 5 months was 3.6±0.3 points on the Ashworth scale in the Tr group and 1.8±0.7 points in the TrGel group. Throughout the observation period, significant differences in FS between groups were observed only in 5 weeks after SCI, whereas significant differences in SS were observed in 2, 3 and 6-8 weeks post-injury. Glial fibrous tissue containing newly formed nerve fibers, isolated or grouped in small clusters, that originated from the surrounding spinal cord matter have been found between the implanted hydrogel fragments. In conclusion, PHPMA-hydrogel improves recovery of the hindlimb locomotor function and promotes regenerative growth of nerve fibers. Further research is needed to clarify the mechanism of this PHPMA-hydrogel effect.

RESUMEN: La regeneración de la médula espinal después de una lesión mecánica es uno de los problemas biomédicos más difíciles. Este artículo evalúa el efecto del hidrogel de poli (N- [2-hidroxipropil] -metacrilamida) (PHPMA-hidrogel) sobre la regeneración de la médula espinal en ratas jóvenes después de la hemiescisión lateral de la médula espinal (lesión) a nivel de los segmentos T12 - T13 (Grupo TrGel). La puntuación de la función locomotora (FS) y la puntuación de espasticidad parética de las patas traseras (SS) se evaluaron de acuerdo con las escalas de Basso- Beattie-Bresnahan (BBB) y Ashworth, respectivamente, y se compararon con un grupo de animales sin matriz implantada (grupo Tr). Se evaluó la regeneración de las fibras nerviosas al nivel de la lesión ~ 5 meses después de la lesión de la médula espinal (LME). Una semana después de la inducción de SCI, el FS en la escala BBB fue 0,9 ± 0,5 puntos en el grupo Tr y 3,6 ± 1,2 puntos en el grupo TrGel. En el grupo Tr, el FS en 5 meses fue significativamente menor que en 2 semanas después de SCI, mientras que no se detectaron cambios significativos en FS en el grupo TrGel durante el período de observación. El FS final fue de 0,8 ± 0,3 puntos en el grupo Tr y de 4,5 ± 1,8 puntos en el grupo TrGel. No se han obser- vado cambios significativos en SS en el grupo TrGel durante el experimento, mientras que el grupo Tr mostró aumentos significativos en SS en la 2ª semana, 6ª semana, 3º mes y 5º mes. La SS en 5 meses fue de 3,6 ± 0,3 puntos en la escala de Ashworth en el grupo Tr y de 1,8 ± 0,7 puntos en el grupo TrGel. A lo largo del período de observación, se observaron diferencias significativas en FS entre los grupos solo en 5 semanas después de la LME, mientras que se observaron diferencias significativas en SS en 2, 3 y 6-8 semanas después de la lesión. Entre los fragmentos de hidrogel implantados se observó tejido fibroso glial que contenía fibras nerviosas recién formadas, aisladas o agrupadas en pequeños grupos, que se originaban a partir de la materia de la médula espinal circundante. En conclusión, PHPMA-hydrogel mejora la recuperación de la función locomotora de las patas traseras y promueve el crecimiento regenerativo de las fibras nerviosas. Se requieren más estudios para aclarar el mecanismo del efecto de hidrogel PHPMA.

Actualización en la fisiopatología y manejo de traumatismo raquimedular: revisión bibliográfica / Actualization in pathophysiology and management of traumatic spinal cord injury: literature review

El Traumatismo Raquimedular (TRM) implica todas las lesiones traumáticas que dañan los huesos, ligamentos, músculos, cartílagos, estructuras vasculares, radiculares o meníngeas a cualquier nivel de la médula espinal. Las consecuencias personales, familiares, sociales y económicas de esta enfermedad, hacen que sea un tema relevante en la actualidad. El propósito de esta revisión es entregar al lector las herramientas elementales sobre el TRM, y está principalmente enfocada en el tratamiento, el cual se aborda estrechamente relacionado con la fisiopatología para comprender los mecanismos moleculares y biomecánicos de trauma, incluyendo sus complicaciones y el manejo de éstas. Respecto al tratamiento del TRM, se aborda la evidencia que ofrecen las terapias actualmente validadas y las aún controversiales, incluyendo los glucocorticoides, la reducción cerrada y la cirugía precoz. Además las terapias emergentes como la hipotermia terapéutica, los nuevos agentes neuroprotectores que se encuentran en fases preclínicas y clínicas de estudio como el riluzol, la minociclina, el litio, los antagonistas opioides, entre otros, y los agentes neurorregenerativos como el Cethrin y el Anti-Nogo que han mostrado buenos resultados en la recuperación neurológica. Las recomendaciones actuales respecto a la terapia con células madre y subtipos de células madre en la actualidad, es que deben llevarse a cabo sólo en el contexto de ensayos clínicos. Aunque aún no existen terapias que permitan la recuperación neurológica completa en todos o la mayoría de los pacientes, las terapias emergentes prevén un futuro promisorio en los resultados clínicos de los pacientes con TRM.

The traumatic spinal cord injury (TSCI) involves all traumatic injuries that harm the bones, ligaments, muscles, cartilage, vascular, radicular or meningeal structures, at any level of the spinal cord. The personal, family, social and economic consequences of this disease, make it an important issue today. The purpose of this review is to provide the reader, the basic tools of the TRM, and it is mainly aimed at the treatment, which it approaches closely related to the pathophysiology, to understand the molecular and biomechanical mechanisms of trauma, including its complications and his management. Regarding treatment of TSCI, the evidence offered by currently validated and controversial therapies is discussed, including glucocorticoids, closed reduction and early surgery. Also emerging therapies such as therapeutic hypothermia, new neuroprotective agents currently in preclinical and clinical phases as riluzole, minocycline, lithium, opioid antagonists, among others, and neuroregenerative agents like Cethrin and Anti- Nogo that have shown good results in neurological recovery. Current recommendations for therapy with stem cells and subtype stem cell, is that only should be carried out in the context of clinical trials. Although there are not still therapies that allow full neurological recovery in all or most patients, emerging therapies provide a promising future in the clinical outcomes of patients with TRM.

Olfactory bulb transplantation in complete spinal cord injury: axonal regeneration and locomotor recovery / Transplante de bulbo olfatório em lesão medular completa: regeneração axonal e recuperação locomotora / Trasplante de bulbo olfatorio en lesiones medulares completas: regeneración axonal y recuperación locomotora

OBJECTIVES: To determine whether the intervention in rats is effective in terms of spinal cord regeneration and locomotor recovery, in order to obtain sufficient evidence to apply the therapy in humans. METHODS: a randomized, controlled, experimental, prospective, randomized trial was conducted, with a sample of 15 adult female Sprague-Dawley rats weighing 250 gr. They were divided into three equal groups, and trained for 2 weeks based on Pavlov's classical conditioning method, to strengthen the muscles of the 4 legs, stimulate the rats mentally, and keep them healthy for the surgery. RESULTS: It was observed that implantation of these cells into the site of injury may be beneficial to the process of spinal cord regeneration after spinal trauma, to mediate secretion of neurotrophic and neuroprotective chemokines, and that the OECs have the ability to bridge the repair site and decrease the formation of gliosis, creating a favorable environment for axonal regeneration. CONCLUSION: It is emphasized that the olfactory ensheathing glial cells possess unique regenerative properties; however, it was not until recently that the activity of promoting central nervous system regeneration was recognized. .

OBJETIVOS: Verificar se intervenção em ratos tem eficácia comprovada na regeneração medular e na recuperação locomotora, visando obter evidência suficiente para aplicar a terapia ao ser humano. MÉTODOS: Estudo prospectivo experimental controlado e randomizado, com amostra de 15 ratas Sprague-Dawley adultas pesando 250 gramas. Os indivíduos foram divididos em três grupos que foram treinados durante 2 semanas pelo método de Pavlov de condicionamento clássico, de modo a fortalecer os músculos das quatro patas, estimular os animais mentalmente e mantê-los saudáveis para a cirurgia. RESULTADOS: Constatou-se que a implantação dessas células no local da lesão pode ser benéfica para o processo de regeneração medular depois do trauma, visto que medeia secreção de quimiocinas neurotróficas e neuroprotetoras; da mesma maneira que as células olfatórias da glia (OEC) têm a capacidade de fazer ponto no local do reparo e de diminuir a formação de gliose, criando ambiente propício para a regeneração axonal. CONCLUSÃO: Cabe destacar que as células olfatórias da glia têm propriedades regeneradoras únicas, porém, apenas recentemente sua atividade promotora de regeneração do sistema nervoso central foi reconhecida. .

OBJETIVOS: Si la intervención en ratas prueba su efectividad respecto a la regeneración medular y la recuperación locomotora con el fin de obtener evidencia suficiente para aplicar la terapia en humanos. MÉTODOS: Se realizóun estudio prospectivo experimental controlado aleatorizado, donde se incluyóuna muestra de 15 ratas adultas hembras Sprague-Dawley de 250 gr. Se dividieron por tercias las cuales se entrenaron durante 2 semanas en base al método de Pavlov de condicionamiento clásico con el fin de fortalecer los músculos de las 4 patas, estimularlas anímicamente y mantenerlas saludables para el acto quirúrgico. RESULTADOS: Se ha observado que el implante de estas células en el sitio de la lesión, puede resultar benéfico para el proceso de regeneración medular después del trauma al mediar la secreción de quimiocinas neurotróficas y neuroprotectoras, asímismo las OECs poseen la habilidad de puentear el sitio de reparación y disminuir la formación de gliosis creando un ambiente permisivo para la regeneración axonal. CONCLUSIÓN: Cabe destacar que las células de la glia olfatoria poseen propiedades regeneradoras únicas, sin embargo no fue sino hasta hace poco que su actividad promotora de regeneración del sistema nervioso central se reconoció. .

Current perspectives in stem cell therapy for spinal cord repair in humans: a review of work from the past 10 years / Atuais perspectivas da terapia com células tronco para regeneração medular em humanos: um revisão de trabalhos dos últimos 10 anos

Spinal cord injury (SCI) and amyotrophic laterals sclerosis (ALS) are devastating neurological conditions that affect individuals worldwide, significantly reducing quality of life, both for patients and their relatives. Objective : The present review aims to summarize the multiple restorative approaches being developed for spinal cord repair, the use of different stem cell types and the current knowledge regarding stem cell therapy. Method : Review of the literature from the past 10 years of human studies using stem cell transplantation as the main therapy, with or without adjuvant therapies. Conclusion : The current review offers an overview of the state of the art regarding spinal cord restoration, and serves as a starting point for future studies. .

Lesão medular (LM) e esclerose lateral amiotrófica (ELA) são condições devastadoras que acometem pessoas em todo o mundo, reduzindo a qualidade de vida tanto de pacientes como de entes queridos. Objetivo : A atual revisão tem como alvo as múltiplas abordagens restauradoras para a regeneração medular, o uso de diferentes tipos celulares e o atual conhecimento a cerca da terapia com células tronco. Método : Revisão de literatura dos últimos 10 anos usando transplantes de células tronco como estratégia principal, com ou sem terapia adjuvante, em humanos. Conclusão : A presente revisão oferece uma visão geral acerca da restauração medular e serve de ponto de partida para estudos futuros. .

Safety Profile, Feasibility and Early Clinical Outcome of Cotransplantation of Olfactory Mucosa and Bone Marrow Stem Cells in Chronic Spinal Cord Injury Patients

STUDY DESIGN: Prospective case series. PURPOSE: To study the safety and feasibility of cotransplantation of bone marrow stem cells and autologous olfactory mucosa in chronic spinal cord injury. OVERVIEW OF LITERATURE: Stem cell therapies are a novel method in the attempt to restitute heavily damaged tissues. We discuss our experience with this modality in postspinal cord injury paraplegics. METHODS: The study includes 9 dorsal spine injury patients with American Spinal Injury Association (ASIA) Impairment Scale (AIS) A neurological impairment who underwent de-tethering of the spinal cord followed by cotransplantation with bone marrow stem cells and an olfactory mucosal graft. Participants were evaluated at the baseline and at 6 monthly intervals. Safety and tolerability were evaluated through the monitoring for adverse events and magnetic resonance imaging evaluation. Efficacy assessment was done through neurological and functional outcome measures. RESULTS: Surgery was tolerated well by all participants. No significant difference in the ASIA score was observed, although differences in the Functional Independence Measure and Modified Ashworth Scale were statistically significant. No significant complication was observed in any of our patients, except for neurogenic pain in one participant. The follow-up magnetic resonance imaging evaluation revealed an increase in the length of myelomalacia in seven participants. CONCLUSIONS: The cotransplantation of bone marrow stem cells and olfactory mucosa is a safe, feasible and viable procedure in AIS A participants with thoracic level injuries, as assessed at the 24-month follow-up. No efficacy could be demonstrated. For application, further large-scale multicenter studies are needed.

Therapeutic approaches for spinal cord injury

This study reviews the literature concerning possible therapeutic approaches for spinal cord injury. Spinal cord injury is a disabling and irreversible condition that has high economic and social costs. There are both primary and secondary mechanisms of damage to the spinal cord. The primary lesion is the mechanical injury itself. The secondary lesion results from one or more biochemical and cellular processes that are triggered by the primary lesion. The frustration of health professionals in treating a severe spinal cord injury was described in 1700 BC in an Egyptian surgical papyrus that was translated by Edwin Smith; the papyrus reported spinal fractures as a ''disease that should not be treated.'' Over the last biological or pharmacological treatment method. Science is unraveling the mechanisms of cell protection and neuroregeneration, but clinically, we only provide supportive care for patients with spinal cord injuries. By combining these treatments, researchers attempt to enhance the functional recovery of patients with spinal cord injuries. Advances in the last decade have allowed us to encourage the development of experimental studies in the field of spinal cord regeneration. The combination of several therapeutic strategies should, at minimum, allow for partial functional recoveries for these patients, which could improve their quality of life.

Lentiviral vector-mediated RNA interfere gene Nogo receptor to repair spinal cord injury / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the effects of lentiviral vector-mediated RNA interfere gene Nogo receptor (NgR) of rat cortical neurons in repairing spinal cord injury.</p><p><b>METHODS</b>The recombinant-lentiviral vector with small inferring RNA siNgR199 which had been constructed was transfected into rat cortical neuron cells in vitro in 3 multiplicity of infection (MOI). The infection rate was determined with fluorescent microscope, and the target gene was detected by PCR analysis. Then, the recombinant was injected into the cortical motor area of the rats with severe spinal cord injury, and the saline was also injected into other rats with severe spinal cord injury as a match control. The functional recovery of the rats' hindlimb was assessed using BBB score and the nerve fiber of the injured region was observed by nerve tracing.</p><p><b>RESULTS</b>The rate of recombinant infecting rat cortical neuron in vitro exceeded 99%. PCR analysis confirmed that the effect of lentiviral vector-mediated RNA interfering gene NgR of rat cortical neurons in vitro was 61%. Although all rats with spinal cord injury were observed to have the hindlimb functional recovery, these rats injected with recombinant had better hindlimb functional recovery than others showing by more BBB score (P < 0.01). Moreover, it was found that some nerve fiber passed the injured spinal cord region of the rats which were injected with recombinant.</p><p><b>CONCLUSION</b>The recombinant lentiviral vector with siNgR199 which had been constructed is able to promote the growth of nerve fiber and the functional recovery of the rats' hindlimb.</p>

Regeneration and Outcome Measures in Spinal Cord Injury

Spinal cord injury (SCI) often results in devastating neurological dysfunction. Therefore many of the SCI patients suffer with physical disabilities or social handicaps. Many obstacles have been known to affect adult spinal cord regeneration and functional recovery. However, scientific knowledge of the central nervous system (CNS) development and post-injury responses including pathophysiology of SCI has been expanded recently, which might produce potential promising therapies for this condition. These are as followed; (1) pharmacological neuroprotective agents, (2) administration of exogenous neurotrophic factors or augmenting intraneural cyclic AMP, (3) inhibition of nonpermissive environment of the injured spinal cord, (4) cellular transplantation, and (5) rehabilitation interventions with body-weight supported treadmill therapy and functional electrical stimulation. In addition, the precise evaluation of functional improvement or gait is also important in rehabilitation of SCI patients. Various evaluation tools have been developed and introduced in order to estimate a degree of improvement properly.

Spinal Cord Regeneration in Rat using Neural Stem Cell Differentiated from Human Telencephalon / 대한정형외과학회잡지

PURPOSE: To evaluate the effect of neural stem cells differentiated from a human telencephalon on the neural regeneration in the severed spinal cord. MATERIALS AND METHODS: The 1st surgery involving the insertion of plastic membrane in the transected cord was performed to prevent spontaneous healing of adult female rats (n=20, 171-237 g) with a complete spinal cord transection. The media was inserted only after removing the previously inserted plastic membrane in the control group (n=6). In the experimental group (n=14), media and neural stem cell (1x) were transplanted after removing the membrane, and immunohistochemical staining was performed. The experimental group was perfused transcardially 5 weeks after the 2nd surgery, and the level of neural cell regeneration determined by immunohistochemical staining. In behavioral analysis, the Basso-Beatie-Bresnahan (BBB) scores of the control and experimental group were compared weekly from immediately after the injury until 5 weeks post-injury after the 2nd surgery. RESULTS: Immunohistochemical stain revealed no neural regeneration in the control group. On the other hand, the survival of transplanted human neural stem cells and remarkable neural regeneration (differentiate to neuron and astrocyte) were observed in the experimental group. In the BBB locomotor scale, the experimental group showed significant recovery in terms of control; and the score increased from postoperative 2 weeks to 3 weeks, and reached a plateau from 3 weeks to 5 weeks. CONCLUSION: The effect of neural stem cells differentiated from human telencephalon on cord regeneration does not produce functional recovery in the BBB locomotor scale, but there is slight recovery of the muscle function. The survival of transplanted human neural stem cells and the possibility of differentiation to neurons or astrocytes were observed.

cDNA microarray analysis of spinal cord injury and regeneration related genes in rat / 生理学报

The acute traumatic spinal cord injury (SCI) is a commonly seen and severe case in clinic. However, the repair and regeneration of injured spinal cord is limited. This is likely due to that different kinds of factors are involved in regeneration after SCI. In the present study, we used complementary DNA microarray consisting of 4 041 specific probes from rat to identify genes that were differentially expressed after SCI. The animals were subjected to complete transection injury of the thoracic spinal cord (T8-T9). Sham operated animals received only a laminectomy. Four and a half days later, rat spinal cord was dissected out for total RNA isolation. The fluorescent (Cy3 and Cy5) labeled probes were prepared and hybridized to the microarray. Genes that showed 2-fold difference in SCI tissue were identified. Sixty-five up-regulated genes consisted of 21 known genes, 30 known expressed sequence tags (ESTs) and 14 unknown genes. Seventy-nine down-regulated genes comprised 20 known genes, 42 known ESTs and 17 unknown genes. In 41 differentially expressed known genes, 5 up-regulated genes, i.e., tissue inhibitor of metalloproteinase 1 (Timp1), transgelin (Tagln), vimentin (Vim), Fc gamma receptor, cathepsin S (Ctss), and 3 down-regulated genes, i.e., stearyl-CoA desaturase, coagulation factor II (F2), endosulfin alpha (Ensa), were further confirmed by reverse transcription polymerase chain reaction (RT-PCR). These genes may play a role in the response to tissue damage or repair following SCI and characterization of them might be helpful to elucidate the molecular mechanisms of spinal cord injury and regeneration.

Effects of embryonic neural stem cells and glial cell line-derived neurotrophic factor in the repair of spinal cord injury / 生理学报

The ability of implanted embryonic neural stem cells (NSCs) to improve survival, migration, and functional recovery following a compression spinal cord injury (SCI) was tested in adult rats. NSCs were isolated from E14-16 rat cerebral cortex and SCI was produced by using an aneurysm clip applicator applied to the 8th thoracic spinal cord according to method of Dolan and Tator. Two weeks after the injury, NSCs (4 microl of 1 x 10(4) cells/microl) were injected into the lesion site. The grafted NSCs were noted to survive and integrate with the host spinal cord 1 month after transplantation, which was demonstrated by the presence of Hoechst 33342 (a nuclear dye) pre-labeled NSCs within and surrounding the lesion site. Some of these cells remained undifferentiated and were stained with nestin, a marker for NSCs. Transplanted NSCs migrated for at least 3 mm from the injury epicenter towards both the rostral and caudal directions. Significant reduction in the lesion area (P<0.05) and improvement in inclined plane (P<0.05) and BBB locomotor rating scale (P<0.05) were found in the cases that received implantation of NSCs, as compared with those that received vehicle injection. More importantly, when glial cell line-derived neurotrophic factor (GDNF; 1.5 microg/microl) was added to the transplants, further reduction in lesion area (P<0.01) and improvement in the function were observed in the combined treatment group as compared with the vehicle infused group. Our results suggest that intraspinal treatment with NSCs and GDNF synergistically reduced lesion size and improved functional outcome after a compressive SCI in adult rats.

Growth Factors and Their Clinical Applications / 대한척추외과학회지

Growth factor is a polypeptide regulating cell proliferation, maturation, activity, and apoptosis. Despite its small molecular weight, it exerts diverse and potent biologic effects on cellular function. With recent development of molecular biology and vector technology, it is now possible to administer recombinant growth factors in clinical dose and modify somatic cell with growth factor encoding gene. Research fields in spinal surgery can be divided into spinal fusion, disc regeneration and spinal cord regeneration. In this review, we discuss the action mechanism of growth factors and their possible clinical applications especially in the field of spinal fusion and disc regeneration.