Neuroprotective effect of deferoxamine on erastininduced ferroptosis in primary cortical neurons.

The iron chelator deferoxamine has been shown to inhibit ferroptosis in spinal cord injury. However, it is unclear whether deferoxamine directly protects neurons from ferroptotic cell death. By comparing the survival rate and morphology of primary neurons and SH-SY5Y cells exposed to erastin, it was found that these cell types respond differentially to the duration and concentration of erastin treatment. Therefore, we studied the mechanisms of ferroptosis using primary cortical neurons from E16 mouse embryos. After treatment with 50 µM erastin for 48 hours, reactive oxygen species levels increased, and the expression of the cystine/glutamate antiporter system light chain and glutathione peroxidase 4 decreased. Pretreatment with deferoxamine for 12 hours inhibited these changes, reduced cell death, and ameliorated cellular morphology. Pretreatment with the apoptosis inhibitor Z-DEVD-FMK or the necroptosis inhibitor necrostain-1 for 12 hours did not protect against erastin-induced ferroptosis. Only deferoxamine protected the primary cortical neurons from ferroptosis induced by erastin, confirming the specificity of the in vitro ferroptosis model. This study was approved by the Animal Ethics Committee at the Institute of Radiation Medicine of the Chinese Academy of Medical Sciences, China (approval No. DWLL-20180913) on September 13, 2018.

Bone marrow mesenchymal stem cells stimulated with low-intensity pulsed ultrasound: Better choice of transplantation treatment for spinal cord injury: Treatment for SCI by LIPUS-BMSCs transplantation.

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.

The association of rs11190870 near LBX1 with the susceptibility and severity of AIS, a meta-analysis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is the most common structural deformity of the spine. Genetics constitute largely to AIS, and the rs11190870 polymorphism has the potential for use in public health and clinical settings as a predictor of AIS risk. The aim of the present meta-analysis was to provide exhaustive evidence to evaluate the association of rs11190870 with the susceptibility and severity of adolescent idiopathic scoliosis (AIS) in multiple ethnic groups and different genders. MATERIALS AND METHODS: The professional databases, including PubMed, Embase, Social Sciences Citation Index, CINAHL, and International Bibliography of the Social Sciences, were searched from 1966 to October 2015. No language restriction was applied. Reference lists of all the selected articles were hand-searched for any additional studies. Three authors independently extracted data from all eligible studies. The data were analyzed by meta-analysis using fixed-effects or random-effects models with mean differences and risk ratios for continuous and dichotomous variables, respectively. RESULTS: Eight studies were included, and the pooled analysis suggested that the T genotype of SNP rs11190870 leads to a higher risk of AIS in multiple ethnic groups regardless of gender (Total:OR, 1.66, 95% CI 1.53, 1.79; I2 = 37.3%, P = 0.000, Female: OR, 1.62, 95% CI 1.50, 1.73; I2 = 26.7%, P = 0.000, Male: OR, 1.79, 95% CI 1.38, 2.20; I2 = 0.00%, P = 0.000). Additionally, the TT and TC genotype had a larger Cobb angle than those with the CC genotype in the overall and female Asian populations. CONCLUSION: A significant association of rs11190870 with AIS was observed in multiple ethnic groups regardless of gender. Additionally, a significant association was found between rs11190870 and curve severity in the overall and female Asian populations. Due to the limited data and clinical heterogeneity, further studies with large sample sizes are required.

Circular RNA GRB10 as a competitive endogenous RNA regulating nucleus pulposus cells death in degenerative intervertebral disk.

Intervertebral disc degeneration (IDD) is an important factor leading to low back pain, but the underlying mechanisms remain poorly understood. Compared with normal nucleus pulposus (NP) tissues, the expression of circ-GRB10 was downregulated in IDD. Furthermore, overexpression of circ-GRB10 inhibited NP cell apoptosis. circ-GRB10 could sequester miR-328-5p, which could potentially lead to the upregulation of target genes related to cell proliferation via the ErbB pathway. In conclusion, the present study revealed that circ-GRB10/miR-328-5p/ERBB2 signaling pathway is involved in IDD development, suggesting that circ-GRB10 might be a novel therapeutic target for IDD.

Discover cervical disc arthroplasty versus anterior cervical discectomy and fusion in symptomatic cervical disc diseases: A meta-analysis.

OBJECTIVE: Symptomatic cervical disc disease (SCDD) is a common degenerative disease, and Discover artificial cervical disc, a new-generation nonconstrained artificial disk, has been developed and performed gradually to treat it. We performed this meta-analysis to compare the efficacy and safety between Discover cervical disc arthroplasty (DCDA) and anterior cervical discectomy and fusion (ACDF) for SCDD. METHODS: An exhaustive literature search of PubMed, EMBASE, and the Cochrane Library was conducted to identify randomized controlled trials that compared DCDA with ACDF for patients suffering SCDD. A random-effect model was used. Results were reported as standardized mean difference or risk ratio with 95% confidence interval. RESULTS: Of 33 articles identified, six studies were included. Compared with ACDF, DCDA demonstrated shorter operation time (P < 0.0001), and better range of motion (ROM) at the operative level (P < 0.00001). But no significant differences were observed in blood loss, neck disability index (NDI) scores, neck and arm pain scores, Japanese orthopaedic association (JOA) scores, secondary surgery procedures and adverse events (P > 0.05). Subgroup analyses did not demonstrated significant differences. CONCLUSION: In conclusion, DCDA presented shorter operation time, and better ROM at the operative level. However, no significant differences were observed in blood loss, NDI scores, neck and arm pain scores, JOA scores, secondary surgery procedures and adverse events between the two groups. Additionally, more studies of high quality with mid- to long-term follow-up are required in future.

Cervical disc arthroplasty for symptomatic cervical disc disease: Traditional and Bayesian meta-analysis with trial sequential analysis.

OBJECTIVE: Cervical disc arthroplasty (CDA) has been designed as a substitute for anterior cervical discectomy and fusion (ACDF) in the treatment of symptomatic cervical disc disease (CDD). Several researchers have compared CDA with ACDF for the treatment of symptomatic CDD; however, the findings of these studies are inconclusive. Using recently published evidence, this meta-analysis was conducted to further verify the benefits and harms of using CDA for treatment of symptomatic CDD. METHODS: Relevant trials were identified by searching the PubMed, EMBASE, and Cochrane Library databases. Outcomes were reported as odds ratio or standardized mean difference. Both traditional frequentist and Bayesian approaches were used to synthesize evidence within random-effects models. Trial sequential analysis (TSA) was applied to test the robustness of our findings and obtain more conservative estimates. RESULTS: Nineteen trials were included. The findings of this meta-analysis demonstrated better overall, neck disability index (NDI), and neurological success; lower NDI and neck and arm pain scores; higher 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores; more patient satisfaction; greater range of motion at the operative level; and fewer secondary surgical procedures (all P < 0.05) in the CDA group compared with the ACDF group. CDA was not significantly different from ACDF in the rate of adverse events (P > 0.05). TSA of overall success suggested that the cumulative z-curve crossed both the conventional boundary and the trial sequential monitoring boundary for benefit, indicating sufficient and conclusive evidence had been ascertained. CONCLUSIONS: For treating symptomatic CDD, CDA was superior to ACDF in terms of overall, NDI, and neurological success; NDI and neck and arm pain scores; SF-36 PCS and MCS scores; patient satisfaction; ROM at the operative level; and secondary surgical procedures rate. Additionally, there was no significant difference between CDA and ACDF in the rate of adverse events. However, as the CDA procedure is a relatively newer operative technique, long-term results and evaluation are necessary before CDA is routinely used in clinical practice.

The carcinogenicity of alendronate in patients with osteoporosis: evidence from cohort studies.

CONTEXT: Alendronate may relate to the incidence of cancers, especially esophageal and colon cancer. But the results are inconsistent in different studies. OBJECTIVE: To quantify the association between the use of alendronate and the occurrence of different types of cancer. DATA SOURCES: We searched Embase, Pubmed, CENTRAL, SIGLE and clinicaltrials.gov, up to 2014 June. STUDY SELECTION: Cohort studies reporting association between alendronate or bisphosphonate therapy including alendronate in patients with osteoporosis and risk of cancer were selected by two authors. DATA EXTRACTION: Two authors independently extracted the data. The Chi-square test and the I-square test were used for testing heterogeneity between studies. DATA SYNTHESIS: Eight cohort studies were included in the meta-analysis. Meta-analysis result manifested that alendronate significantly increased the incidence of lung cancer (HR 1.23, 95%CI 1.03 to 1.47, P value = 0.03), nevertheless, there was no significant difference after we excluded either Lee's 2012 study (HR 1.17, 95%CI 0.95 to 1.44, P value = 0.13) or Chiang's 2012 study (HR 1.47, 95%CI 1 to 2.17, P value = 0.05). For the incidence of colorectal cancer, no significant difference occurred (HR 0.91, 95%CI 0.74 to 1.13, P value = 0.39), but there was a positive relationship when we used fixed model (HR 0.85, 95%CI 0.78 to 0.93, P value = 0.004). For the incidence of liver cancer, there was no significant difference (HR 1.36, 95%CI 0.9 to 2.04, P value = 0.14), however, the result changed after we excluded Chiang's 2012 study (HR 1.69, 95%CI 1.03 to 2.77, P value = 0.04). There was no significant difference in other types of cancer. CONCLUSION: Based on current evidences, alendronate therapy may be associated with a high risk of lung cancer, may with an excess risk of liver cancer, a low risk of colorectal and no related risk of other cancers.

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

PURPOSE: To compare the clinical and radiographic results of fixed-bearing and mobile-bearing total knee arthroplasty (TKA). METHODS: We 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. RESULTS: A total of 24 studies involving 2,799 patients were identified in this analysis. Meta-analysis showed lower pain score (OR, 0.66, 95% 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, 95% CI: -0.60, 0.26), range of movement (SMD, -0.05, 95% CI: -0.63, 0.53), radiolucent line (OR, 1.03, 95% CI 0.74, 1.44), patient preference (OR, 1.15, 95% CI 0.82, 1.61), walking support (OR, 1.07, 95% CI 0.68, 1.70), and complications (OR, 0.85, 95% CI 0.59, 1.21). CONCLUSIONS: The 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 EVIDENCE: II.

Tourniquet used in anterior cruciate ligament reconstruction: a system review.

PURPOSE: To identify whether routine use of a tourniquet is a better choice for anterior cruciate ligament reconstruction. METHOD: We searched Amed, British Nursing Index, Embase, Pubmed, Scopus, Cochrane Library and Google Scholar. We used revised Jadad score to evaluate the trial quality. Each reference list was viewed for any ignored studies. Two reviews independently extracted data from all eligible trials, including study design, patients' characteristics, interventions and outcomes. The available data were using random effects models with mean differences for continuous variables. RESULTS: The only meta-analysis indicated there was no significant difference in operative time between the tourniquet and non-tourniquet groups (mean differences -5.71, 95 % CI -12.40, 0.99). The remaining outcomes had variations in the outcome measures, so it was not possible to perform meta-analysis. CONCLUSIONS: There was insufficient evidence to support the hypothesis that patients would benefit from routinely applying a tourniquet. More high-quality randomized controlled trials were needed to test the result.

Evidence-based computer-navigated total hip arthroplasty: an updated analysis of randomized controlled trials.

BACKGROUND: Total hip arthroplasty (THA) has evolved over the years to be a reliable, reproducible, and successful orthopedic procedure. Nowadays, THA is increasingly performed on patients using less invasive, tissue-preserving techniques. Accordingly, the use of computer navigation in total joint arthroplasty has become more prevalent. However, there is still lack of high-quality evidence to verify the most effective technique for THA. METHODS: A search was conducted in PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar databases. Clinical trials published from 1966 to Feb 2012 that assess conventional techniques THA or computer-navigated techniques THA for placing the acetabular component. The main outcome measures included abduction angles, anteversion angles, percentage of acetabular outliers, operation time, decrease in Hb/24 h, and wound secretion/48 h. RESULTS: The pooled analysis across all studies showed a significant difference in anteversion angles and acetabular outliers (difference -0.22, 95% CI -0.67, 0.24; p = 0.346, I (2) = 71.9%) and (difference 8.34, 95% CI 4.15, 16.74; p = 0.000, I (2) = 0.0%). However, no significant difference in abduction angle and decrease in Hb/24 h (difference -0.22, 95% CI -0.67, 0.24; p = 0.346, I (2) = 71.9%) and (difference 0.03, 95% CI -0.36, 0.41; p = 0.888, I (2) = 0.0%). For the operation time, computer-navigated THA was longer (difference -0.73, 95% CI -1.32, -0.15; p = 0.014, I (2) = 74.4%). CONCLUSIONS: This meta-analysis demonstrated computer-navigated THA was a more favorable method for placing the acetabular component and decreased the number of acetabular cups implanted outside the desired range of alignment. More high-quality RCTs were needed to support the evidence.

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

OBJECTIVES: To compare the outcomes of cemented and uncemented hemiarthroplasty for treating displaced femoral neck fractures. METHOD: We 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. RESULTS: A total of 12 studies involving 1805 patients were identified in this analysis. Meta-analysis showed longer operation time (SMD, -0.43, 95 % 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, 95 % CI 0.88, 1.34), hospital stay (SMD, -1.21, 95 % CI -2.24, -0.18), blood loss (SMD, -0.12, 95 % CI -0.33, 0.10), operation time (SMD, -0.43, 95 % CI -0.56, -0.30), residual pain (OR, 1.42, 95 % CI 0.99, 2.03), and complications (OR, 0.82, 95 % CI 0.63, 1.08). CONCLUSIONS: The available evidence suggested there was no significant difference between uncemented and cemented hemiarthroplasty in treating displaced femoral neck fractures.

Forked osteotomy arthroplasty for elbow tuberculosis: six years of follow-up.

BACKGROUND: Elbow tuberculosis (TB) is not rare in China. Most patients are diagnosed when it is at an advanced stage and with bony ankylosis complications. For a developing country, such as China, it is important for there to be safe and cost-effective procedures. MATERIALS AND METHODS: A retrospective study was designed to assess the effects of improved forked excision arthroplasty for treating elbow TB. There were 20 patients (average age, 48.45 years). For all patients, the preoperative diagnosis was elbow TB at an advanced stage. All patients underwent forked excision arthroplasty. Patients were evaluated preoperatively and postoperatively with the Mayo's elbow performance score (MEPS). Mean follow-up was at 74.4 months. RESULTS: At the last follow-up, the mean postoperative MEPS was 83.7 compared with the preoperative MEPS of 20.25. Results of Mayo's elbow performance index were excellent in seven patients, good in 12 and fair in one, and none were poor. The range of elbow motion also improved significantly. CONCLUSION: This study of forked elbow excision arthroplasty has shown promising results for treating elbow TB. Most patients had ideal postoperative outcomes and exhibited painless elbow joints, with satisfactory functional recovery at medium-term follow-up. Further studies with longer follow-up are warranted. LEVEL OF EVIDENCE: III.

[The efficacy analysis of selective decompression of lumbar root canal of elderly lumbar spinal stenosis].

OBJECTIVE: To evaluate the effect of the treatments of lumbar spinal stenosis by selective decompression of lumbar root canal and laminectomy. METHODS: From March 2007 to March 2011, 144 lumbar spinal stenosis patients were treated by selective decompression of lumbosacral root canal and laminectomy. All of these patients included 64 male and 80 female patients, age range 60-87 years, average (66 ± 5) years. Duration 6-72 months, average (12 ± 16) months. The patients were divided into 2 groups according to surgical procedure underwent: group A including 70 patients who were treated with selective decompression of lumbar root canal, group B including 74 patients who were treated with traditional laminectomy. Five time points were selected to assess clinical effect using Oswestry disability index (ODI) and Japanese Orthopaedic Association (JOA), which were pre-operation and 1 month, 6 months, 12 months and last follow-up. The data were analyzed through Wilcoxon matched-pairs signed-ranks test. RESULTS: All operations were completed well without severe complications. The duration of follow-up was 12-55 months, average (31 ± 6) months. All patients' symptoms got improved or partial remission. The average pre- and post-operative scores of JOA in group A and B were from 14.0 ± 1.6 to 20.3 ± 1.7, from 13.6 ± 1.7 to 20.2 ± 2.0, respectively, there were significant statistical differences (Z = 2.41 and 2.23, P < 0.05). The average pre- and post-operative scores of ODI in group A and B were from 62% ± 4% to 28% ± 4%, from 63% ± 4% to 27% ± 3%, respectively, there were significant statistical differences (Z = 2.93 and 2.64, P < 0.05). CONCLUSIONS: Personalized treatment programs should be established for elderly lumbar spinal stenosis according to stenosis location. Laminectomy is carried out with the stenosis in the central spinal canal; selective decompression of lumbosacral root canal is accepted with the stenosis in the nerve root canal without central stenosis.

Factors affecting the length of stay of patients with traumatic spinal cord injury in Tianjin, China.

PURPOSE: To describe the acute care length of stay (ACLOS) of adult patients with traumatic spinal cord injury (TSCI) in Tianjin, China, and identify the associated demographic and clinical factors. METHODS: TSCI patients admitted to a general hospital in Tianjin, China from 2004 to 2007 were identified. The predictor variables were demographic and clinical factors, including age, gender, etiology, level of injury, severity, associated injuries, surgery, and complications. The outcome variable was ACLOS. Multivariable linear regression analysis models were used to examine the association between predictor and outcome variables. RESULTS: This study included 631 TSCI patients. The mean ACLOS was 32.4 ± 37.7 days, with a range of 1-294 days. The median number of hospitalization days was 21 days. Admission to a suburban hospital surgery, urinary infection, poorer functional status, pressure ulcers, and associated injuries were significantly associated with ACLOS. CONCLUSION: This study examined the effect of epidemiological and clinical factors on ACLOS in Tianjin, China. The factors that influenced the ACLOS were different from factors reported in other studies. More studies are needed in China to determine the effect of these factors on ACLOS in TSCI patients and to propose a predictive model.

Cryptococcosis of lumbar vertebra in a patient with rheumatoid arthritis and scleroderma: case report and literature review.

BACKGROUND: Although cryptococcosis mainly occurs in the central nervous system and lungs in immunocompromised hosts, it can involve any body site or structure. Here we report the first case of primary cryptococcosis of a lumbar vertebra without involvement of the central nervous system or lungs in a relatively immunocompromised individual with rheumatoid arthritis and scleroderma. CASE PRESENTATION: A 40-year-old Chinese woman with rheumatoid arthritis diagnosed 1 year beforehand and with a subsequent diagnosis of scleroderma was found to have an isolated cryptococcal infection of the fourth lumbar vertebra. Her main complaints were severe low back and left leg pain. Cryptococcosis was diagnosed by CT-guided needle biopsy and microbiological confirmation; however, serum cryptococcal antigen titer was negative. After 3 months of antifungal therapy with fluconazole the patient developed symptoms and signs of scleroderma, which was confirmed on laboratory tests. After taking fluconazole for 6 months, the progressive destruction of the lumbar vertebral body had halted and the size of an adjacent paravertebral mass had decreased substantially. On discharge symptoms had resolved and at an annual follow-up there was no evidence of recurrence on the basis of symptoms, signs or imaging investigations. CONCLUSION: Although cryptococcosis of the lumbar vertebra is extremely rare, it should be considered in the differential diagnosis for patients with lumbar vertebral masses to avoid missed diagnosis, misdiagnosis and diagnostic delay. Early treatment with antifungals proved to be a satisfactory alternative to surgery in this relatively immunocompromised patient. Any residual spinal instability can be treated later, once the infection has resolved.

Treatment of three- and four-part proximal humeral fractures with locking proximal humerus plate.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness and complications of the locking proximal humerus plate to treat proximal humerus fractures. DESIGN: A retrospective clinical trial. SETTING: Department of Orthopaedics, Tianjin Medical University General Hospital. PATIENTS: Sixty-eight consecutive patients with three- or four-part fractures of the proximal humerus were treated with locking proximal humerus plates. INTERVENTION: The deltopectoral anterolateral acromial approach was used to the proximal humerus; open reduction and locking proximal humerus plate were applied. MAIN OUTCOME MEASUREMENTS: Constant Score was used to measure the shoulder functional recovery, and Visual Analog Scale (VAS) was used to measure subjective evaluation of pain. The radiology was observed. RESULTS: After average 26.7 months, the average Constant Score was 72.6 ± 13.2 points and the average VAS was 1.2 ± 0.8 points. All the complications such as screw perforation into the glenohumeral joint, screws loosening, soft tissue infections, avascular necrosis and delayed union occurred in eight cases (11.8 %). CONCLUSIONS: The effectiveness of the locking proximal humerus plate was similar to other published literatures on treating fractures of the proximal humerus; however, a lower complications rate in short follow-up time was observed in this study. It may potentially provide a favorable option for treating three- or four-part fractures of the proximal humerus. Dealing with each particular fracture pattern, surgeons should have a decision of appropriate way to internal fixation.

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

AIM: We 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. MATERIALS & METHODS: ASCs 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 Dulbecco's modified Eagle's 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 Dulbecco's modified Eagle's medium were also transplanted in rats with SCI as a control. Recovery of rat's 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. RESULTS: Using 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. CONCLUSION: Effective 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.

Regeneration of spinal cord with cell and gene therapy.

OBJECTIVE: Transplantation of fetal spinal cord cells (FSCC) can promote regeneration of injured spinal cord, while Schwann cells (SC) and some growth factors have a similar effect. However, the synergistic effects and optimal combination of these modalities have not yet been evaluated. In the current study, the efficiency of cell therapy of FSCC and/or SC, with/without growth factors (nerve growth factor [NGF] and brain-derived neurotrophic factor [BDNF]) was examined, with the aim of establishing an optimized protocol for spinal cord injury. METHODS: One hundred and twenty adult rats were randomly divided into six groups with 20 rats in each group. One week after the thoracic spinal cord injury model had been created, the rats were treated with different therapeutic modalities: Dulbecco's modified Eagles medium (DMEM) in Group I, FSCC in Group II, FSCC plus SC in Group III, FSCC plus SC over-expressing NGF in Group IV, FSCC plus SC over-expressing BDNF in Group V, and FSCC plus SC over-expressing both NGF and BDNF in Group VI. Subsequently, the rats were subjected to behavioral tests once a week after injury, while histology, immunohistochemistry and electron microscopy were performed at one and three month post-operation. RESULTS: Both SC and FSCC promoted regeneration of spinal cord injury when used separately, while a combination of the two types of cell resulted in better recovery than either alone. Both growth factors (NGF and BDNF) enhanced the outcomes of cell therapy, while synergistic effects meant that a combination of each individual component (group VI) achieved the best results according to locomotion scale, histology and immunoreactivity in the injured cords. CONCLUSION: SC, NGF and BDNF can enhance the outcome of FSCC therapy, while the combination of FSC with SC, NGF and BDNF is possibly the optimal protocol for clinical treatment of acute spinal cord injury.