Guang-Zhi Ning

Transplantation of autologous activated Schwann cells in the treatment of spinal cord injury: six cases, more than five years of follow-up.

Schwann cells (SCs) are the main glial cells of the peripheral nervous system, which can promote neural regeneration. Grafting of autologous SCs is one of the well-established and commonly performed procedures for peripheral nerve repair. With the aim to improve the clinical condition of patients with spinal cord injury (SCI), a program of grafting autologous activated Schwann cells (AASCs), as well as a series of appropriate neurorehabilitation programs, was employed to achieve the best therapeutic effects. We selected six patients who had a history of SCI before transplantation. At first, AASCs were obtained by prior ligation of sural nerve and subsequently isolated, cultured, and purified in vitro. Then the patients accepted an operation of laminectomy and cell transplantation, and no severe adverse event was observed in any of these patients. Motor and sensitive improvements were evaluated by means of American Spinal Injury Association (ASIA) grading and Functional Independence Measure (FIM); bladder and urethral function were determined by clinical and urodynamic examination; somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) were used to further confirm the functional recovery following transplantation. The patients were followed up for more than 5 years. All of the patients showed some signs of improvement in autonomic, motor, and sensory function. So we concluded that AASC transplantation might be feasible, safe, and effective to promote neurorestoration of SCI patients.

Epidemiological profile of 239 traumatic spinal cord injury cases over a period of 12 years in Tianjin, China

Abstract Study design Hospital-based retrospective review. Objective To describe the epidemiological characteristics and trends of traumatic spinal cord injury in Tianjin, China. Setting Tianjin Medical University General Hospital. Methods Medical records of 239 patients with traumatic spinal cord injury admitted to a general hospital from 1998 to 2009 were reviewed. Variables included gender, age, marital status, occupation, etiology, time of injury, level, and severity of injury. Epidemiological characteristics of different countries were compared. Results Over this period, the mean age of patients with traumatic spinal cord injury was 45.4 ± 14.1 years, and the male/female ratio was 4.6:1. In all, 86.2% were married. The leading cause was fall (52.3%), followed by motor vehicle collision (36.4%). The most common injury site was the cervical spinal cord, accounting for 82.0%. Incomplete tetraplegia made up for 59.4%, followed by complete tetraplegia (22.6%). Eight patients died after operation, six of whom died from respiratory complications. Conclusion The results of this study are in accordance with that of most other developing countries; falls and motor vehicle collisions were the two leading causes, but the mean age was older. Percentage of the aged with traumatic spinal cord injury was increasing. The low-falls group tended to expand over this period. All these data indicated that the preventive programs should focus on the traffic accidents and falls, and more attention should be paid to the aged for the vulnerability to low fall.

Combination of activated Schwann cells with bone mesenchymal stem cells: the best cell strategy for repair after spinal cord injury in rats.

AIMnWe aim to explore the repair effect of combined cell therapy using activated Schwann cells (ASCs) and bone mesenchymal stem cells (BMSCs) in traumatic spinal cord injury (SCI) in rats.nnnMATERIALS & METHODSnASCs and BMSCs were used for combined transplantation to treat acute SCI in rats, both of which can be obtained from SCI patients. ASCs were obtained by prior ligation of saphenous nerve and BMSCs by flush of the marrow cavity with Dulbeccos modified Eagles medium solution. Our experiment in vitro confirmed that ASCs promoted BMSCs to differentiate into mature neural cells. It also indicates that BMSCs hold the potential to repair CNS injury. ASCs and BMSCs were co-transplanted into the injured epicenter of spinal cord made by the New York University (NYU) impactor machine using a 10 g × 50 mm drop weight. Complete ASCs, BMSCs and Dulbeccos modified Eagles medium were also transplanted in rats with SCI as a control. Recovery of rats hindlimb function was serially evaluated by Basso, Beattie, Bresnahan locomotor rating scale and footprint analysis. Changes of neurological potential were recorded by nerve electrophysiologic test. Improvement in the microenvironment of the injured spinal cord was evaluated by hematoxylin and eosin staining, glial fibrillary acidic protein staining, biotinylated dextran amine anterograde tracing and electron microscopy.nnnRESULTSnUsing biotinylated dextran amine anterograde tracing, we demonstrated that there were more regenerative axons of corticospinal tract surrounding and passing through the injured cavity to the caudal cord in the ASC-BMSC co-graft group than those in the other three groups, and we also confirmed this further by quantitative analysis. Immunostaining for glial fibrillary acidic protein showed the smallest population of astrocytes in the injury epicenter in the ASC-BMSC group compared with the other three groups. Relatively complete myelin sheaths and organelles were found in the ASC-BMSC group compared with the other three groups under electron microscopy.nnnCONCLUSIONnEffective co-transplantation of ASCs and BMSCs promotes functional recovery in rats hindlimbs and reduces the formation of glial scar, and remyelinates the injured axons as compared with the other three groups. This conclusion was also supported by the observation of immunohistochemistry staining and electron microscopy, suggesting the possible clinical application for the treatment of spinal injury.

Intraspinal cord graft of autologous activated Schwann cells efficiently promotes axonal regeneration and functional recovery after rat's spinal cord injury

Basic research in spinal cord injury (SCI) has made great strides in recent years, and some new insights and strategies have been applied in promoting effective axonal regrowth and sprouting. However, a relatively safe and efficient transplantation technique remains undetermined. This study, therefore, was aimed to address a question of how to graft Schwann cells to achieve the best possible therapeutic effects. To clarify the issue, the rats were subjected to spinal cord injury at T10. Autologous activated Schwann cells (AASCs) were obtained by prior ligation of saphenous nerve and subsequently isolated and purified in vitro and then grafted into spinal cord-injured rats via three different routes (group I: intravenous, group II: intrathecal and group III: intraspinal cord). Neurologic function was serially evaluated by Basso, Beattie, Bresnahan locomotor rating scale and footprint analysis. We also evaluated the migration of the transplanted cells at 2 weeks after transplantation. Using biotinylated dextran amine (BDA) anterograde tracing, we demonstrated that more regenerative axons of corticospinal tract (CST) surrounding the injured cavity in group III than those in the other two groups, and we also confirmed it further by quantitative analysis. The microenvironment surrounding the injured spinal cord has been improved to the greatest extent in group III, as determined by immunohistological staining. Relatively complete myelin sheaths and more neurofilaments in axons were found in groups II and III than those in group I under electron microscopy. The results showed that intraspinal cord injection of AASCs promoted recovery of hindlimb locomotor function of injured rats more efficiently than the other grafting routes. In addition, intact myelin sheaths and sufficient neurofilaments in axons were not adequate for full functional recovery after SCI, suggesting that reestablishment of normal synaptic connection is indispensable. The findings in this study strongly suggest that transplantation of AASCs directly into the spinal cord may be one of the promising candidates for potential scaffold for injured spinal cord, and such strategy of transplantation of AASCs could be hopeful to treat patients with SCI.

All-trans retinoic acid prevents epidural fibrosis through NF-κB signaling pathway in post-laminectomy rats

Laminectomy is a widely accepted treatment for lumbar disorders, and epidural fibrosis (EF) is a common complication. EF is thought to cause post-operative pain recurrence after laminectomy or discectomy. All-trans retinoic acid (ATRA) has shown anti-fibrotic, anti-inflammatory, and anti-proliferative functions. The object of this study was to investigate the effects of ATRA on the prevention of EF in post-laminectomy rats. In vitro, the anti-fibrotic effect of ATRA was demonstrated with cultured fibroblasts count, which comprised of those that were cultured with/without ATRA. In vivo, rats underwent laminectomy at the L1-L2 levels. We first demonstrated the beneficial effects using 0.05% ATRA compared to vehicle (control group). We found that a higher concentration of ATRA (0.1%) achieved dose-dependent results. Hydroxyproline content, Rydell score, vimentin-positive cell density, fibroblast density, inflammatory cell density and inflammatory factor expression levels all suggested better outcomes in the 0.1% ATRA rats compared to the other three groups. Presumably, these effects involved ATRAs ability to suppress transforming growth factor (TGF-β1) and interleukin (IL)-6 which was confirmed with reverse-transcriptase polymerase chain reaction (RT-PCR). Finally we demonstrated that ATRA down-regulated nuclear factor (NF)-κB by immunohistochemistry and western blotting for p65 and inhibition of κB (IκBα), respectively. Our findings indicate that topical application of ATRA can inhibit fibroblast proliferation, decrease TGF-β1 and IL-6 expression level, and prevent epidural scar adhesion in rats. The highest concentration employed in this study (0.1%) was the most effective. ATRA suppressed EF through down-regulating NF-κB signaling, whose specific mechanism is suppression of IκB phosphorylation and proteolytic degradation.

Comparative efficacy and tolerability of three treatments in old people with osteoporotic vertebral compression fracture: a network meta-analysis and systematic review.

Purpose The question which kind of methods is most suitable for treating the old people for osteoporotic vertebral compression fracture is still discussed and pairwise meta-analyses cannot get hierarchies of these treatments. Our aim is to integrate the evidence to provide hierarchies of the comparative efficacy measured by the change of VAS (Visual Analogue Scale) and tolerability measured by incidence of new fractures and risk of all-cause discontinuation on three treatments (percutaneous vertebroplasty (PVP)、balloon kyphoplasty (BK) and conservative treatment(CT)). Methods We performed a Bayesian-framework network meta-analysis of randomized controlled trials (RCTs) to compare three treatments for the old people with osteoporotic vertebral compression fracture. The eligible RCTs were identified by searching Amed, British Nursing Index, Embase, Pubmed, the Cochrane Central Register of Controlled Trials (CENTRAL), Google scholar, SIGLE, the National Technical Information Service, the National Research Register (UK) and the Current Controlled Trials databases. Data from three outcomes (e.g. VAS, risk of all-cause discontinuation and incidence of new fractures) were independently extracted by two authors. Results A total of five RCTs were finally included into this article. PVP and BK significantly decreased VAS when compared with CT. BK had a significantly lower risk of all-cause discontinuation contrast to CT. Three treatments (BK, PVP and CT) had no significant differences in the incidence of new fractures. Conclusions PVP may be the best way to relieve pain, CT might lead to the lowest incidence of new fractures and BK might had the lowest risk of all-cause discontinuation in old people with osteoporotic vertebral compression fracture. More large-scale and longer duration of follow-up studies are needed.

Epidemiology of traumatic spinal cord injury in Asia: A systematic review

Abstract Study design A systematic review. Background The number of traumatic spinal cord injury (TSCI) reports grows annually, especially in China and Korea. The epidemiological characteristics of TSCI in Asia differ from those in other countries. Thus, we compiled epidemiological factors from Asia to compare with those from other countries. Method We searched articles published in any language between January 1980 to December 2011 using the terms “spinal cord injury”, “traumatic spinal cord injury”, “epidemiology”, and “Asia”. The articles were reviewed for information regarding TSCI incidence, total cases, case criteria, case source, causes of injury, male/female ratio, mean age, prospective or retrospective, neurological level of injury, extent of injury, and America Spinal Injury Association Impairment Scale (AIS)/grade. Results Epidemiological data were extracted from 39 reports in the published literature that met the inclusion criteria. Only two studies reported prevalence rates. Incidence rates ranged from 12.06 to 61.6 per million. The average age ranged from 26.8 to 56.6 years old. Men were at higher risk than women. Motor vehicle collisions (MVCs) and falls were the main causes of TSCI. However, several countries reported war wounds as the major cause. The neurological level and extent of injury were mixed, and most patients were categorized as AIS/Frankel grade A. Conclusion TSCI is an important public health problem and a major cause of paralysis. We must understand the epidemiology to implement appropriate preventative measures. Asian epidemiology is different from that in other regions, so intervention measures must be established according to population-specific characteristics.

Cemented versus uncemented hemiarthroplasty for displaced femoral neck fractures: an updated meta-analysis

ObjectivesTo compare the outcomes of cemented and uncemented hemiarthroplasty for treating displaced femoral neck fractures.MethodWe searched the PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar databases from 1966 to Mar 2012. No language restriction was applied. Reference lists of all the selected articles were hand-searched for any additional trials. Trial quality was assessed using the modified Jadad Scale. Two authors independently extracted data from all eligible studies, including study design, participants, interventions, and outcomes (mortality, hospital stay, blood loss, operation time, residual pain, and complications). The data were using fixed-effects and random-effects models with mean differences and risk ratios for continuous and dichotomous variables, respectively.ResultsA total of 12 studies involving 1805 patients were identified in this analysis. Meta-analysis showed longer operation time (SMD, −0.43, 95xa0% CI −0.56, −0.30) in cemented versus uncemented hemiarthroplasty. There was no significant difference between the two treatment groups regarding mortality (OR, 1.08, 95xa0% CI 0.88, 1.34), hospital stay (SMD, −1.21, 95xa0% CI −2.24, −0.18), blood loss (SMD, −0.12, 95xa0% CI −0.33, 0.10), operation time (SMD, −0.43, 95xa0% CI −0.56, −0.30), residual pain (OR, 1.42, 95xa0% CI 0.99, 2.03), and complications (OR, 0.82, 95xa0% CI 0.63, 1.08).ConclusionsThe available evidence suggested there was no significant difference between uncemented and cemented hemiarthroplasty in treating displaced femoral neck fractures.

No difference in clinical outcome between fixed- and mobile-bearing TKA: a meta-analysis

PurposeTo compare the clinical and radiographic results of fixed-bearing and mobile-bearing total knee arthroplasty (TKA).MethodsWe searched the PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar databases from 1966 to January 2012. No language restriction was applied. Reference lists of all the selected articles were hand-searched for any additional trials. Trial quality was assessed using the modified Jadad scale. Two authors independently extracted data from all eligible studies, including study design, participants, interventions, and outcomes (Knee Society Score, range of movement, radiolucent line, patient preference, walking support, pain score, and complications). The data were using fixed-effects or random-effects models with mean differences and risk ratios for continuous and dichotomous variables, respectively.ResultsA total of 24 studies involving 2,799 patients were identified in this analysis. Meta-analysis showed lower pain score (OR, 0.66, 95xa0% CI 0.46, 0.94) in mobile-bearing TKA than fixed-bearing TKA. There was no significant difference between the two treatment groups regarding Knee Society Score (SMD, −0.17, 95xa0% CI: −0.60, 0.26), range of movement (SMD, −0.05, 95xa0% CI: −0.63, 0.53), radiolucent line (OR, 1.03, 95xa0% CI 0.74, 1.44), patient preference (OR, 1.15, 95xa0% CI 0.82, 1.61), walking support (OR, 1.07, 95xa0% CI 0.68, 1.70), and complications (OR, 0.85, 95xa0% CI 0.59, 1.21).ConclusionsThe available evidence suggested that there was no significant difference between clinical and radiographic results of fixed-bearing and mobile-bearing TKA except for pain score. Regarding clinical relevance, the less incidence of pain could be the advantage for selecting mobile-bearing TKA.Level of evidenceII.

Targeting RPTPσ with lentiviral shRNA promotes neurites outgrowth of cortical neurons and improves functional recovery in a rat spinal cord contusion model.

After spinal cord injury (SCI), the rapidly upregulated chondroitin sulfate proteoglycans (CSPGs), the prominent chemical constituents and main repulsive factors of the glial scar, play an important role in the extremely limited ability to regenerate in adult mammals. Although many methods to overcome the inhibition have been tested, no successful method with clinical feasibility has been devised to date. It was recently discovered that receptor protein tyrosine phosphatase sigma (RPTPσ) is a functional receptor for CSPGs-mediated inhibition. In view of the potential clinical application of RNA interference (RNAi), here we investigated whether silencing RPTPσ via lentivirus-mediated RNA interference can promote axon regeneration and functional recovery after SCI. Neurites of primary rat cerebral cortical neurons with depleted RPTPσ exhibited a significant enhancement in elongation and crossing ability when they encountered CSPGs in vitro. A contusion model of spinal cord injury in Wistar rats (the New York University (NYU) impactor) was used for in vivo experiments. Local injection of lentivirus encoding RPTPσ shRNA at the lesion site promoted axon regeneration and synapse formation, but did not affect the scar formation. Meanwhile, in vivo functional recovery (motor and sensory) was also enhanced after RPTPσ depletion. Therefore, strategies directed at silencing RPTPσ by RNAi may prove to be a beneficial, efficient and valuable approach for the treatment of SCI.