Summary Stem cells are considered to be one of the greatest potential treatments to cure degenerative diseases. Stem cells injection for knee osteoarthritis (OA) is still a relatively new treatment and has not yet gained popularity. So, the effectiveness, safety and potential of mesenchymal stem cells (MSCs) for knee OA treatment is worthy to be explored. Explore the effectiveness and safety of mesenchymal stem cells (MSCs) in the treatment of knee osteoarthritis. We collected clinical trials using MSCs as treatment for knee OA (before April 2019), including randomized controlled trials (RCTs), retrospective studies and cohort studies. We searched PubMed, EMBASE, Cochrane Library, Web of Science and the ClinicalTrials.gov with keywords (Mesenchymal stem cells [MSCs], Knee osteoarthritis, Effectiveness and Safety), and then performed a systematic review and cumulative metaanalysis of all RCTs and retrospective comparative studies. To evaluate the effectiveness and safety of MSC in knee OA treatment, we applied visual analog scale score, Western Ontario and McMaster Universities Osteo-arthritis Index and adverse events. We included 15 RCTs, two retrospective studies and two cohort studies including a total of 584 knee OA patients in this study. We demonstrated that MSC treatment could significantly decrease visual analog scale in a 12-month follow-up study compared with controls (p < 0.001). MSC therapy also showed significant decreases in Western Ontario and McMaster Universities Osteoarthritis Index scores after the 6-month follow-up (p < 0.001). MSC therapy showed no difference compared with controls (p > 0.05) in adverse events. We suggest that MSC therapy could serve as an effective and safe therapy for clinical application in OA treatment. The translational potential of this article This study provided the best available evidence and a wider perspective to MSCs application in the management of knee OA. MSCs therapy will have great translational potential in the clinical treatment of various degenerative diseases once optimum formula and explicit target population are identified.
Osteosarcoma (OS) is a malignant disease that develops rapidly and is associated with poor prognosis. Immunotherapy may provide new insights into clinical treatment strategies for OS. The purpose of this study was to identify immune-related genes that could predict OS prognosis. The gene expression profiles and clinical data of 84 OS patients were obtained from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. According to non-negative matrix factorization, two molecular subtypes of immune-related genes, C1 and C2, were acquired, and 597 differentially expressed genes between C1 and C2 were identified. Univariate Cox analysis was performed to get 14 genes associated with survival, and 4 genes (GJA5, APBB1IP, NPC2, and FKBP11) obtained through least absolute shrinkage and selection operator (LASSO)-Cox regression were used to construct a 4-gene signature as a prognostic risk model. The results showed that high FKBP11 expression was correlated with high risk (a risk factor), and that high GJA5, APBB1IP, or NPC2 expression was associated with low risk (protective factors). The testing cohort and entire TARGET cohort were used for internal verification, and the independent GSE21257 cohort was used for external validation. The study suggested that the model we constructed was reliable and performed well in predicting OS risk. The functional enrichment of the signature was studied through gene set enrichment analysis, and it was found that the risk score was related to the immune pathway. In summary, our comprehensive study found that the 4-gene signature could be used to predict OS prognosis, and new biomarkers of great significance for understanding the therapeutic targets of OS were identified.
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