Background: This study aimed to investigate the effect of bone marrow mesenchymal stem cell (BMSC)-derived exosome injection on cartilage damage and pain relief in both in vitro and in vivo models of osteoarthritis (OA). Methods: The BMSCs were extracted from rat bone marrow of the femur and tibia. Chondrocytes were treated with IL-1β to establish the in vitro model of OA. Chondrocyte proliferation and migration were assessed by CCK-8 and transwell assay, respectively. A rat model of OA was established by injection of sodium iodoacetate. At 6 weeks after the model was established, the knee joint specimens and dorsal root ganglion (DRG) of rats were collected for histologic analyses. For pain assessment, paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were evaluated before model establishment and at 1, 2, 4, and 6 weeks after model establishment. Results: Exosomes can be endocytosed with the chondrocytes in vitro. Exosome treatment significantly attenuated the inhibitory effect of IL-1β on the proliferation and migration of chondrocytes. Exosome pre-treatment significantly attenuated IL-1β-induced downregulation of COL2A1 and ACAN and upregulation of MMP13 and ADAMTS5. In the animal study, exosome treatment significantly upregulated COL2A1 protein and downregulated MMP13 protein in the cartilage tissue of the OA rat. At weeks 2, 4, and 6, the PWL value was significantly improved in the exosome-treated OA rats as compared with the untreated OA animals. Moreover, exosome treatment significantly alleviated the upregulation of CGRP and iNOS in the DRG tissue of OA rats. Conclusion: BMSC-derived exosomes can effectively promote cartilage repair and extracellular matrix synthesis, as well as alleviate knee pain in the OA rats.

Background: This study employs systematic review and meta-analysis to explore the incidence and characteristics of spinal cord injury (SCI) between 2000 and 2021, aiming to provide the most recent and comprehensive data support for the prevention, diagnosis, treatment, and care of SCI. Methods: Systematic searches were conducted on epidemiological studies of SCI published between January 1, 2000, and March 29, 2024. Meta-analysis, subgroup analysis, meta-regression, publication bias detection, and literature quality assessment were extensively utilized. Results: The pooled results from 229 studies indicated that the overall incidence rate of SCI was 23.77 (95% CI, 21.50–26.15) per million people, with traumatic spinal cord injuries (TSCI) at a rate of 26.48 (95% CI, 24.15–28.93) per million people, and non-traumatic spinal cord injuries (NTSCI) at a rate of 17.93 (95% CI, 13.30-23.26) per million people. The incidence of TSCI exhibited a marked age-related increase and was significantly higher in community settings compared to hospital and database sources. Males experienced TSCI at a rate 3.2 times higher than females. Between 2000 and 2021, the incidence of TSCI remained consistently high, between 20 and 45 per million people, whereas NTSCI incidence has seen a steady rise since 2007, stabilizing at a high rate of 25–35 per million people. Additionally, the incidence of TSCI in developing countries was notably higher than that in developed countries. There were significant differences in the causes of injury, severity, injury segments, gender, and age distribution among the TSCI and NTSCI populations, but the proportion of male patients was much higher than that of female patients. Moreover, study quality, country type, and SCI type contributed to the heterogeneity in the meta-analysis. Conclusions: The incidence rates of different types of SCI remain high, and the demographic distribution of SCI patients is changing, indicating a serious disease burden on healthcare systems and affected populations. These findings underscore the necessity of adopting targeted preventive, therapeutic, and rehabilitative measures based on the incidence and characteristics of SCI.

Ferroptosis is a newly discovered form of iron-dependent oxidative cell death and drives the loss of neurons in spinal cord injury (SCI). Mitochondrial damage is a critical contributor to neuronal death, while mitochondrial quality control (MQC) is an essential process for maintaining mitochondrial homeostasis to promote neuronal survival. However, the role of MQC in neuronal ferroptosis has not been clearly elucidated. Here, we further demonstrate that neurons primarily suffer from ferroptosis in SCI at the single-cell RNA sequencing level. Mechanistically, disordered MQC aggravates ferroptosis through excessive mitochondrial fission and mitophagy. Furthermore, mesenchymal stem cells (MSCs)-mediated mitochondrial transfer restores neuronal mitochondria pool and inhibits ferroptosis through mitochondrial fusion by intercellular tunneling nanotubes. Collectively, these results not only suggest that neuronal ferroptosis is regulated in an MQC-dependent manner, but also fulfill the molecular mechanism by which MSCs attenuate neuronal ferroptosis at the subcellular organelle level. More importantly, it provides a promising clinical translation strategy based on stem cell-mediated mitochondrial therapy for mitochondria-related central nervous system disorders.

OBJECTIVE: A prospective randomized controlled study was conducted to clarify whether percutaneous transforaminal endoscopic discectomy (PTED) results in better clinical outcomes and less surgical trauma than microendoscopic discectomy (MED).METHODS: In this single-center, open-label, randomized controlled trial, patients were included if they had persistent signs and symptoms of radiculopathy with corresponding imaging-confirmed lumbar disc herniation. Patients were randomly allocated to the PTED or the MED group by computer-generated randomization codes. The primary outcome was the Oswestry Disability Index (ODI) score 1 year after surgery. Secondary outcomes included scores of the Medical Outcomes Study 36-Item Short-Form Health Survey bodily pain and physical function scales, EuroQol Group’s EQ-5D , and the visual analog scales for back pain and leg pain. Data including duration of operation, in-bed time, length of hospital stay, surgical cost and total hospital cost, complications, and reoperations were recorded.RESULTS: A total of 153 participants were randomly assigned to 2 treatment groups (PTED vs MED), and 89.5% (137 patients) completed 1 year of follow-up. Primary and secondary outcomes did not differ significantly between the treatment groups at each prespecified follow-up point (p > 0.05). For PTED, there was less postoperative improvement in ODI score in the median herniation subgroup at 1 week (p = 0.027), 3 months (p = 0.013), 6 months (p = 0.027), and 1 year (p = 0.028) compared with the paramedian subgroup. For MED, there was significantly less improvement in ODI score at 3 months (p = 0.008), 6 months (p = 0.028), and 1 year (p = 0.028) in the far-lateral herniation subgroup compared with the paramedian subgroup. The total complication rate over the course of 1 year was 13.75% in the PTED group and 16.44% in the MED group (p = 0.642). Five patients (6.25%) in the PTED group and 3 patients (4.11%) in the MED group suffered from residue/recurrence of herniation, for which reoperation was required.CONCLUSIONS: Over the 1-year follow-up period, PTED did not show superior clinical outcomes and did not seem to be a safer procedure for patients with lumbar disc herniation compared with MED. PTED had inferior results for median disc herniation, whereas MED did not seem to be the best treatment option for far-lateral disc herniation.Clinical trial registration no.: NCT01997086 (clinicaltrials.gov).

Background: Although exosomes, as byproducts of human umbilical cord mesenchymal stem cells (hUC-MSCs), have been demonstrated to be an effective therapy for traumatic spinal cord injury (SCI), their mechanism of action remains unclear. Methods: We designed and performed this study to determine whether exosomes attenuate the lesion size of SCI by ameliorating neuronal injury induced by a secondary inflammatory storm and promoting neurite outgrowth. We determined the absolute levels of all exosomal miRNAs and investigated the potential mechanisms of action of miR-199a-3p/145-5p in inducing neurite outgrowth in vivo and in vitro. Results: miR-199a-3p/145-5p, which are relatively highly expressed miRNAs in exosomes, promoted PC12 cell differentiation suppressed by lipopolysaccharide (LPS) in vitro through modulation of the NGF/TrkA pathway. We also demonstrated that Cblb was a direct target of miR-199a-3p and that Cbl was a direct target of miR-145-5p. Cblb and Cbl gene knockdown resulted in significantly decreased TrkA ubiquitination levels, subsequently activating the NGF/TrkA downstream pathways Akt and Erk. Conversely, overexpression of Cblb and Cbl was associated with significantly increased TrkA ubiquitination level, subsequently inactivating the NGF/TrkA downstream pathways Akt and Erk. Western blot and coimmunoprecipitation assays confirmed the direct interaction between TrkA and Cblb and TrkA and Cbl. In an in vivo experiment, exosomal miR-199a-3p/145-5p was found to upregulate TrkA expression at the lesion site and also promote locomotor function in SCI rats. Conclusions: In summary, our study showed that exosomes transferring miR-199a-3p/145-5p into neurons in SCI rats affected TrkA ubiquitination and promoted the NGF/TrkA signaling pathway, indicating that hUC-MSC-derived exosomes may be a promising treatment strategy for SCI.