Disulfidptosis decoded: a journey through cell death mysteries, regulatory networks, disease paradigms and future directions.

Cell death is an important part of the life cycle, serving as a foundation for both the orderly development and the maintenance of physiological equilibrium within organisms. This process is fundamental, as it eliminates senescent, impaired, or aberrant cells while also promoting tissue regeneration and immunological responses. A novel paradigm of programmed cell death, known as disulfidptosis, has recently emerged in the scientific circle. Disulfidptosis is defined as the accumulation of cystine by cancer cells with high expression of the solute carrier family 7 member 11 (SLC7A11) during glucose starvation. This accumulation causes extensive disulfide linkages between F-actins, resulting in their contraction and subsequent detachment from the cellular membrane, triggering cellular death. The RAC1-WRC axis is involved in this phenomenon. Disulfidptosis sparked growing interest due to its potential applications in a variety of pathologies, particularly oncology, neurodegenerative disorders, and metabolic anomalies. Nonetheless, the complexities of its regulatory pathways remain elusive, and its precise molecular targets have yet to be definitively identified. This manuscript aims to meticulously dissect the historical evolution, molecular underpinnings, regulatory frameworks, and potential implications of disulfidptosis in various disease contexts, illuminating its promise as a groundbreaking therapeutic pathway and target.

Epigenetic regulation and factors that influence the effect of iPSCs-derived neural stem/progenitor cells (NS/PCs) in the treatment of spinal cord injury.

Spinal cord injury (SCI) is a severe neurological disorder that causes neurological impairment and disability. Neural stem/progenitor cells (NS/PCs) derived from induced pluripotent stem cells (iPSCs) represent a promising cell therapy strategy for spinal cord regeneration and repair. However, iPSC-derived NS/PCs face many challenges and issues in SCI therapy; one of the most significant challenges is epigenetic regulation and that factors that influence this mechanism. Epigenetics refers to the regulation of gene expression and function by DNA methylation, histone modification, and chromatin structure without changing the DNA sequence. Previous research has shown that epigenetics plays a crucial role in the generation, differentiation, and transplantation of iPSCs, and can influence the quality, safety, and outcome of transplanted cells. In this study, we review the effects of epigenetic regulation and various influencing factors on the role of iPSC-derived NS/PCs in SCI therapy at multiple levels, including epigenetic reprogramming, regulation, and the adaptation of iPSCs during generation, differentiation, and transplantation, as well as the impact of other therapeutic tools (e.g., drugs, electrical stimulation, and scaffolds) on the epigenetic status of transplanted cells. We summarize our main findings and insights in this field and identify future challenges and directions that need to be addressed and explored.

Syringaresinol promotes the recovery of spinal cord injury by inhibiting neuron apoptosis via activating the ubiquitination factor E4B/AKT Serine/Threonine kinase signal pathway.

Spinal cord injury (SCI) is a serious traumatic disease with no effective treatment. This study aimed to explore the therapeutic effect of syringaresinol on SCI. First, the potential targets and associated signaling pathways of syringaresinol were predicted by bioinformatics analysis and molecular docking. Second, MTT was employed to evaluate cell proliferation rate, Western blot was performed to detect protein expression, RT-qPCR was conducted to detect mRNA expression levels, flow cytometry and 5-ethynyl-2'-deoxyuridine (EDU) staining were used to determine cell apoptosis, and immunofluorescence and immunohistochemistry were used to estimate the expression of RNA binding fox-1 homolog 3 and clipped caspase 3. Basso-Beattie-Bresnahan scores and inclined plate tests were conducted to analyze hindlimb locomotor function. Results showed that syringaresinol could inhibit the apoptosis of glutamate-treated SHSY5Y cells by upregulating the expression of ubiquitination factor E4B (UBE4B) and activating the AKT serine/threonine kinase (AKT) signaling pathway. This effect can be rescued by UBE4B knockdown or AKT pathway inhibition. Syringaresinol remarkably improved locomotor function and increased neuronal survival in SCI rats. Our results suggested that syringaresinol could promote locomotor functional recovery by reducing neuronal apoptosis by activating the UBE4B/AKT signaling pathway.

Epidemiological updates of post-traumatic related limb osteomyelitis in china: a 10 years multicentre cohort study.

BACKGROUND: Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China. METHODS: The study was approved by the Institutional Research Board (IRB), and 3526 PTRLO patients were identified from 212 394 traumatic limb fracture patients at 21 hospitals between 1 January 2008 and 31 December 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors and antibiotic resistance and sensitivity. RESULTS: The IR of PTRLO increased gradually from 0.93 to 2.16% (Z=14.392, P <0.001). Monomicrobial infection (82.6%) was significantly higher than polymicrobial infection (17.4%) ( P <0.001). The IR of Gram-positive (GP) and Gram-negative (GN) pathogens showed a significant increase from the lowest 0.41% to the highest 1.15% (GP) or 1.62% (GN), respectively. However, the longitudinal trend of GP vs. GN's composition did not show any significance (Z=±1.1918, P >0.05). The most prevalent GP strains were Methicillin-sensitive Staphylococcus aureus (MSSA) (17.03%), Methicillin-resistant Staphylococcus aureus (MRSA) (10.46%), E. faecalis (5.19%) and S. epidermidis (4.87%). In contrast, the dominant strains GN strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E. coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for polymicrobial infection include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities. CONCLUSIONS: This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).

Han's technique: a new reduction technique for acute anterior shoulder dislocation.

INTRODUCTION: Acute anterior shoulder dislocation (AASD) is the most common joint dislocation. Here, we introduced a new reduction technique for AASD, named "Han's technique" (or "Touch overhead technique"). METHODS: Patients diagnosed with AASD were treated with "Han's technique" in the orthopaedic department of our hospital from October 2018 to November 2020. An orthopedic surgeon performed the reduction maneuver without any anesthesia or sedation throughout the reduction process. The fundamental information and related data were recorded, including patients' age, sex, dislocation side, previous dislocations history, reduction time, number of attempts at reduction, success rate of the reduction, intensity of pain during reduction using the 10-point visual analogue scale score (VAS), any complications, with or without the fracture and neurovascular examination results. RESULTS: Forty-one patients with AASD were involved in our study. Thirty-nine cases (95%) were primary dislocation. Eleven patients (27%) were complicated with large tubercle fracture and one patient (2%) complicated with inferior glenoid fractures. All patients were successfully reduced by Han's technique with mean reduction time was 138 s. The pain score during the reduction operation is only1.83 ± 0.83 points. No neurovascular injury or iatrogenic fracture was found after reduction in all patients. CONCLUSIONS: Han's technique (or Touch overhead technique) is a simple, safe, effective, mild and easy to master which can be operated by one surgeon without anesthesia or sedation for AASD.

Polycaprolactone electrospun fiber scaffold loaded with iPSCs-NSCs and ASCs as a novel tissue engineering scaffold for the treatment of spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a traumatic disease of the central nervous system, accompanied with high incidence and high disability rate. Tissue engineering scaffold can be used as therapeutic systems to provide effective repair for SCI. PURPOSE: In this study, a novel tissue engineering scaffold has been synthesized in order to explore the effect of nerve repair on SCI. PATIENTS AND METHODS: Polycaprolactone (PCL) scaffolds loaded with actived Schwann cells (ASCs) and induced pluripotent stem cells -derived neural stem cells (iPSC-NSCs), a combined cell transplantation strategy, were prepared and characterized. The cell-loaded PCL scaffolds were further utilized for the treatment of SCI in vivo. Histological observation, behavioral evaluation, Western-blot and qRT-PCR were used to investigate the nerve repair of Wistar rats after scaffold transplantation. RESULTS: The iPSCs displayed similar characteristics to embryonic stem cells and were efficiently differentiated into neural stem cells in vitro. The obtained PCL scaffolds werê0.5 mm in thickness with biocompatibility and biodegradability. SEM results indicated that the ASCs and (or) iPS-NSCs grew well on PCL scaffolds. Moreover, transplantation reduced the volume of lesion cavity and improved locomotor recovery of rats. In addition, the degree of spinal cord recovery and remodeling maybe closely related to nerve growth factor and glial cell-derived neurotrophic factor. In summary, our results demonstrated that tissue engineering scaffold treatment could increase tissue remodeling and could promote motor function recovery in a transection SCI model. CONCLUSION: This study provides preliminary evidence for using tissue engineering scaffold as a clinically viable treatment for SCI in the future.

Microenvironment Imbalance of Spinal Cord Injury.

Spinal cord injury (SCI), for which there currently is no cure, is a heavy burden on patient physiology and psychology. The microenvironment of the injured spinal cord is complicated. According to our previous work and the advancements in SCI research, 'microenvironment imbalance' is the main cause of the poor regeneration and recovery of SCI. Microenvironment imbalance is defined as an increase in inhibitory factors and decrease in promoting factors for tissues, cells and molecules at different times and spaces. There are imbalance of hemorrhage and ischemia, glial scar formation, demyelination and re-myelination at the tissue's level. The cellular level imbalance involves an imbalance in the differentiation of endogenous stem cells and the transformation phenotypes of microglia and macrophages. The molecular level includes an imbalance of neurotrophic factors and their pro-peptides, cytokines, and chemokines. The imbalanced microenvironment of the spinal cord impairs regeneration and functional recovery. This review will aid in the understanding of the pathological processes involved in and the development of comprehensive treatments for SCI.

Efficacy and safety of tension band wiring versus plate fixation in olecranon fractures: a systematic review and meta-analysis.

BACKGROUND: Olecranon fracture (OF) is a common upper limb fracture, and the most commonly used techniques are still tension band wiring (TBW) and plate fixation (PF). The aim of the current study is to discuss whether TBW or PF technique of internal fixation is better in the treatment of OFs, using the method of meta-analysis. METHODS: The eligible studies were acquired from PubMed, CNKI, Embase, Cochrane Library, and other sources. The data were extracted by two of the coauthors independently and were analyzed by RevMan5.3. Standardized mean differences (SMDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess risk of bias. RESULTS: Thirteen studies including 1 RCT and 12 observational studies were assessed. Our meta-analysis results showed that both in RCT and observational studies, there were no significant differences between the two groups in disabilities of the arm, shoulder and hand (DASH) (SMD = 0.07, 95% CI = -0.32 to 0.46, p = 0.73), improvement rate (OR = 0.76, 95% CI = 0.48-1.22, p = 0.26), range of motion (ROM), operation time (SMD = -0.51, 95% CI = -1.17 to 0.14, p = 0.12) and blood loss (SMD = -0.97, 95% CI = -2.06 to 0.11, p = 0.08). The overall estimate of complications indicated that the pooled OR was 2.61 (95% CI = 1.65-4.14, p < 0.0001), suggesting that the difference was statistically significant. We also compared the outcomes of patients with mayo type IIA OFs treated by TBW and PF in DASH and ROM and found no differences. CONCLUSIONS: Both TBW and PF interventions had treatment benefit in OFs. The current study reveals that there are no significant differences in DASH, improvement rate, ROM, operation time, and blood loss between TBW and PF for OFs. Due to the less complications, we recommend the PF approach as the optical choice for OFs. More high-quality studies are required to further confirm our results.

Open versus endoscopic in situ decompression in cubital tunnel syndrome: A systematic review and meta-analysis.

OBJECTIVE: We conducted this systematic review and meta-analysis to compare the clinical efficacy and safety between open and endoscopic in situ decompression surgery methods for cubital tunnel syndrome (CuTS). METHODS: PubMed, Medline, Embase, Cochrane Library and CNKI were searched for eligible studies. The data were extracted by two of the coauthors (WL, BYF) independently and were analyzed using RevMan statistical software, version 5.1. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool and the Newcastle-Ottawa Scale were used to assess the risk of bias. RESULTS: Seven studies were included for systematic review, and six studies were included for meta-analysis. The CuTS patients received open in situ decompression (OISD) or endoscopic in situ decompression (EISD). A pooled analysis of postoperative Bishop score showed that the difference was not statistically significant between the EISD group and the OISD group (RR = 0.99, 95% CI = 0.88-1.12, P = 0.88). The overall estimate of postoperative satisfaction between the EISD group and the OISD group was not found to be significant (RR = 0.98, 95% CI = 0.89-1.08, P = 0.70). The overall estimate of complications (RR = 0.88, 95% CI = 0.24-3.29, P = 0.85) suggested that the difference was not statistically significant. CONCLUSIONS: EISD and OISD for treating CuTS have equivalent efficacy for postoperative clinical improvement, whereas the incidences of complications of endoscopic surgical procedure were also same as those with the open surgical procedure. In situ decompression (especially EISD, with minor intraoperative trauma) could be treated as a valuable alternative to treat CuTS.

Does vertebral augmentation lead to an increasing incidence of adjacent vertebral failure? A systematic review and meta-analysis.

BACKGROUND: The aim of the present study was to evaluate whether vertebral augmentation technology increases the occurrence of adjacent vertebral fractures in patients with osteoporotic vertebral compression fractures (OVCFs). MATERIALS AND METHODS: Databases, including MEDLINE, EMBASE and Cochrane library, were retrieved via PRISMA covering 1987 to 2015. The number of patients who suffered from adjacent secondary vertebral fractures was calculated. A meta-analysis, using indexes of odds ratios (OR) and 95% confidence intervals (95% CI), was conducted with STATA software. Subgroup investigations were conducted according to the operation methods and the duration of observation. Sensitivity analysis and publication bias were also evaluated. RESULTS: Ten randomized controlled trials (RCTs) met our inclusion criteria. Our results indicated there was no statistically significant difference in the occurrence rate of adjacent vertebral fractures between manipulation of vertebral augmentation and non-surgical treatment (OR = 0.89, 95% CI = 0.58-1.37). Neither subgroup investigations based on selection of operation nor duration of follow-up time showed marked differences. A sensitivity analysis did not identify specific trails seriously deflected. No obvious publication bias was identified. CONCLUSION: Despite various limitations in the present study, our data demonstrated that using vertebral augmentation was not related to increasing incidence of subsequent adjacent vertebral fractures.

Efficacy, safety, and cost of surgical versus nonsurgical treatment for carpal tunnel syndrome: A systematic review and meta-analysis.

BACKGROUND: Carpal tunnel syndrome (CTS) is a common peripheral nerve entrapment disease. Either surgical or conservative intervention for CTS patients is needed to choose. We conducted this systematic review and meta-analysis to compare the clinical efficacy, safety, and cost of surgical versus nonsurgical intervention. METHODS: The eligible studies were acquired from PubMed, Medline, Embase, Web of Science, Google, and Cochrane Library. The data were extracted by 2 of the coauthors independently and were analyzed by RevMan5.3. Standardized mean differences (SMDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess risk of bias. RESULTS: Thirteen studies including 9 randomized controlled trials (RCTs) and 4 observational studies were assessed. The methodological quality of the trials ranged from moderate to high. The difference of clinical efficacy was statistically significant between surgical and nonsurgical intervention, and nonsurgical treatment was more effective (OR = 2.35, 95%CI = 1.18-4.67, P = 0.01). Meanwhile, different results were discovered by subgroup analysis. The pooled results of function improvement, symptom improvement, neurophysiological parameters improvement, and cost of care at different follow-up times showed that the differences were not statistically significant between the 2 interventions. The difference of complications and side-effects was statistically significant and conservative treatment achieved better result than surgery (OR = 2.03, 95%CI = 1.28-3.22, P = 0.003). Sensitivity analysis proved the stability of the pooled results. CONCLUSION: Both surgical and conservative interventions had benefits in CTS. Nonsurgical treatment was more effective and safety than surgical treatment, but there were no significant differences in function improvement, symptom improvement, neurophysiological parameters improvement, and cost of care. Nonsurgical treatment is recommended as the optical choice for CTS. If conservative treatment fails, surgical release can be taken.

Cannulated screw fixation and plate fixation for displaced intra-articular calcaneus fracture: A meta-analysis of randomized controlled trials.

BACKGROUND: Displaced intra-articular calcaneus fractures (DIACFs) are the most common type of calcaneus fracture. The differences in therapeutic effectiveness between cannulated screw fixation (CSF) and plate fixation are still unclear. Thus, in this meta-analysis, we evaluated the therapeutic effectiveness of these two fixation methods. MATERIALS AND METHODS: We searched for all publications on DIACFs fixated with cannulated screws or plates in the following electronic databases: Pubmed, Cochrane, Embase and CNKI. Only randomized controlled studies were included. The Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0) was applied for analysis. The primary outcomes were American Orthopedic Foot and Ankle Society score (AOFAS), improvement of Bohler's angle, improvement of Gissane's angle and the width of the calcaneus. Outcomes were reported as the standard mean difference (SMD) or relative risk (RR) with the 95% confidence interval (CI). A random effects model was used to assess the pooled data. RESULTS: Five randomized controlled studies met our inclusion criteria, and a total of 707 patients were involved. There was no statistically significant difference between the cannulated screw fixation group and the plate fixation group in terms of excellent and good AOFAS scores (RR = 1.01, 95%CI 0.91 to 1.13, P = 0.79), improvement of Bohler's angle (SMD = 0.12, 95%CI -0.03 to 0.28, P = 0.12), improvement of Gissane's angle (SMD = 0.09, 95%CI -0.28 to 0.26, P = 0.30), or the width of the calcaneus (SMD = -0.07, 95%CI -0.24 to 0.10, p = 0.45). Compared with plate fixation, CSF showed a significant reduction in the duration of surgery (SMD = -1.74, 95%CI, -3.35 to -0.13, P = 0.03) and rate of complications (RR = 0.25, 95%CI, 0.15 to 0.44, P＜0.00001). CONCLUSIONS: Cannulated screw fixation and plate fixation have similar fixation effectiveness and functional outcomes in the treatment of displaced intra-articular calcaneus fractures. Due to the shorter duration of surgery and low rate of complications, cannulated screw fixation is superior to plate fixation. However, further studies are needed to evaluate cannulated screw fixation for various Sanders types of calcaneus fractures.

Identification of microRNAome in rat bladder reveals miR-1949 as a potential inducer of bladder cancer following spinal cord injury.

The costs of spinal cord injury and its complications are high in personal, social and financial terms. Complications include bladder cancer, for which the risk is 16-28 times higher than that of the general population, There is currently little consensus regarding the cause of this discrepancy. As microRNAs are stable biomarkers and potential therapeutic targets of cancer, the present study aimed to explore the underlying mechanisms of this phenomenon by examining changes in the microRNAome. Rats were used to produce models of spinal cord injury. Microarrays and bioinformatics were used to investigate the cancer-associated microRNAs that are upregulated in rat bladders following spinal cord injury. In order to validate the results, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry were performed. The expression of miR-1949 was found to be deregulated and abundant in the rat bladder following spinal cord injury. Bioinformatics demonstrated that retinoblastoma 1, which is involved in tumorigenesis, is a target gene of miR-1949. qRT-PCR, western blotting and immunohistochemistry confirmed the results of the microarray analysis. In addition, it was shown that miR-1949 expression was not influenced by aging. Furthermore, the expression of miR-1949 was stable until the third month following spinal cord injury, after which it significantly increased. If this increase was prolonged, the expression of retinoblastoma 1 may decline to a carcinogenic level. The present study suggests a role for miR-1949 in the translational regulation of retinoblastoma 1 and in subsequent bladder tumorigenesis following spinal cord injury.

The role of the JAK-STAT pathway in neural stem cells, neural progenitor cells and reactive astrocytes after spinal cord injury.

Patients with spinal cord injuries can develop severe neurological damage and dysfunction, which is not only induced by primary but also by secondary injuries. As an evolutionarily conserved pathway of eukaryotes, the JAK-STAT pathway is associated with cell growth, survival, development and differentiation; activation of the JAK-STAT pathway has been previously reported in central nervous system injury. The JAK-STAT pathway is directly associated with neurogenesis and glia scar formation in the injury region. Following injury of the axon, the overexpression and activation of STAT3 is exhibited specifically in protecting neurons. To investigate the role of the JAK-STAT pathway in neuroprotection, we summarized the effect of JAK-STAT pathway in the following three sections: Firstly, the modulation of JAK-STAT pathway in proliferation and differentiation of neural stem cells and neural progenitor cells is discussed; secondly, the time-dependent effect of JAK-STAT pathway in reactive astrocytes to reveal their capability of neuroprotection is revealed and lastly, we focus on how the astrocyte-secretory polypeptides (astrocyte-derived cytokines and trophic factors) accomplish neuroprotection via the JAK-STAT pathway.

Transactivating-transduction protein-polyethylene glycol modified liposomes traverse the blood-spinal cord and blood-brain barriers.

Naive liposomes can cross the blood-brain barrier and blood-spinal cord barrier in small amounts. Liposomes modified by a transactivating-transduction protein can deliver antibiotics for the treatment of acute bacterial infection-induced brain inflammation. Liposomes conjugated with polyethylene glycol have the capability of long-term circulation. In this study we prepared transactivating-transduction protein-polyethylene glycol-modified liposomes labeled with fluorescein isothiocyanate. Thus, liposomes were characterized by transmembrane, long-term circulation and fluorescence tracing. Uptake, cytotoxicity, and the ability of traversing blood-spinal cord and blood-brain barriers were observed following coculture with human breast adenocarcinoma cells (MCF-7). Results demonstrated that the liposomes had good biocompatibility, and low cytotoxicity when cocultured with human breast adenocarcinoma cells. Liposomes could traverse cell membranes and entered the central nervous system and neurocytes through the blood-spinal cord and blood-brain barriers of rats via the systemic circulation. These results verified that fluorescein isothiocyanate-modified transactivating-transduction protein-polyethylene glycol liposomes have the ability to traverse the blood-spinal cord and blood-brain barriers.

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.