Objective: To evaluate the effects and safety of intra-articular injection of mesenchymal stem cells on patients with knee osteoarthritis by a systematic review and meta-analysis. Methods: PubMed, EMBASE, and Cochrane Library were retrieved. An assessment of the risk of bias was done through the Cochrane Collaborative Bias Risk Tool, publication bias was assessed by plotting funnel plots and Egger tests. Pain and functional improvements in patients with knee osteoarthritis were determined by changes in VAS scores and WOMAC scores at baseline and follow-up endpoints. For the evaluation of MRI, the WORMS score and changes in cartilage volume were used. In addition, the number of adverse events in the intervention group and the control group were counted to explore the safety. Results: A total of 10 randomized controlled trials involving 335 patients were included. In the pooled analysis, compared with the control groups, the VAS scores of MSC groups decreased significantly (MD,−19.24; 95% CI: −26.31 to −12.18, P < .00001. All of the WOMAC scores also improved significantly: the total scores (SMD, − 0.66; 95% CI: − 1.09 to −0.23, P = .003), pain scores (SMD, − 0.46; 95% CI: − 0.75 to −0.17, P = .002), stiffness scores (SMD, −0.32; 95% CI: −0.64 to 0.00 P = 0.05), and functional scores (SMD, −0.36; 95% CI: −0.69 to −0.04, P = .03). Two studies with non-double-blind designs were the main source of heterogeneity. In terms of cartilage repair, there was no significant difference in the WORMS score, but there was a significant increase in cartilage volume in the MSC group (SMD, 0.69; 95% CI: 0.25 to 1.13, P = .002). The proportion of patients with adverse events in the MSCs treatment group was significantly higher than that in the control group (OR, 3.20; 95% CI: 1.50 to 6.83, P = .003). Conclusions: Intra-articular injection of mesenchymal stem cells is effective and safety to relieve pain and improve motor function of patients with knee osteoarthritis in a short term which is different to conclusions of previous study.
OBJECTIVE:The aim of this study was to evaluate the effectiveness and safety of stem cell transplantation for spinal cord injury (SCI).DATA SOURCES:PubMed, EMBASE, Cochrane, China National Knowledge Infrastructure, China Science and Technology Journal, Wanfang, and SinoMed databases were systematically searched by computer to select clinical randomized controlled trials using stem cell transplantation to treat SCI, published between each database initiation and July 2016.DATA SELECTION:Randomized controlled trials comparing stem cell transplantation with rehabilitation treatment for patients with SCI. Inclusion criteria: (1) Patients with SCI diagnosed according to the American Spinal Injury Association (ASIA) International standards for neurological classification of SCI; (2) patients with SCI who received only stem cell transplantation therapy or stem cell transplantation combined with rehabilitation therapy; (3) one or more of the following outcomes reported: outcomes concerning neurological function including sensory function and locomotor function, activities of daily living, urination functions, and severity of SCI or adverse effects. Studies comprising patients with complications, without full-text, and preclinical animal models were excluded. Quality of the included studies was evaluated using the Cochrane risk of bias assessment tool and RevMan V5.3 software, provided by the Cochrane Collaboration, was used to perform statistical analysis.OUTCOME MEASURES:ASIA motor score, ASIA light touch score, ASIA pinprick score, ASIA impairment scale grading improvement rate, activities of daily living score, residual urine volume, and adverse events.RESULTS:Ten studies comprising 377 patients were included in the analysis and the overall risk of bias was relatively low level. Four studies did not detail how random sequences were generated, two studies did not clearly state the blinding outcome assessment, two studies lacked blinding outcome assessment, one study lacked follow-up information, and four studies carried out selective reporting. Compared with rehabilitation therapy, stem cell transplantation significantly increased the lower limb light touch score (odds ratio (OR) = 3.43, 95% confidence interval (CI): 0.01 – 6.86, P = 0.05), lower limb pinprick score (OR = 3.93, 95%CI: 0.74 – 7.12, P = 0.02), ASI grading rate (relative risk (RR) = 2.95, 95%CI: 1.64 – 5.29, P = 0.0003), and notably reduced residual urine volume (OR = –8.10, 95%CI: –15.09 to –1.10, P = 0.02). However, stem cell transplantation did not significantly improve motor score (OR = 1.89, 95%CI: –0.25 to 4.03, P = 0.08) or activities of daily living score (OR = 1.12, 95%CI: –1.17 to 4.04, P = 0.45). Furthermore, stem cell transplantation caused a high rate of mild adverse effects (RR = 14.49, 95%CI: 5.34 – 34.08, P < 0.00001); however, these were alleviated in a short time.CONCLUSION:Stem cell transplantation was determined to be an efficient and safe treatment for SCI and simultaneously improved sensory and bladder functions. Although associated ...
Background Microglia participate in mediating neuroinflammation in which P2X7R triggered by adenosine triphosphate has a critical effect after spinal cord injury. However, how the P2X7R of microglia regulate neuroinflammation after spinal cord injury is still unclear. The aim of this study was to explore the mechanism by which the P2X7 receptor of microglia regulates neuroinflammation after spinal cord injury in NLRP3 inflammasome-dependent inflammation. Material/Methods Sixt rats were divided into 5 groups: a sham group, a model group, a BzATP group, an A-438079 group, and a BzATP+CY-09 group. Rats in the sham group were only subjected to laminectomy and rats in the other groups were subjected to spinal cord injury followed by treatment with physiological saline, BzATP, A-438079, and BzATP following CY-09, separately. Real-time polymerase chain reaction, Western blot, immunofluorescence staining, and enzyme-linked immunosorbent assay were used to analyze the scientific hypothesis. Results (i) P2X7R of microglia was upregulated and downregulated by BzATP, and A-438079 was upregulated after spinal cord injury. (ii) Upregulation of P2X7R on microglia is coincident with increase of neuroinflammation after spinal cord injury. (iii) P2X7R of microglia participates in spinal cord-mediated neuroinflammation via regulating NLRP3 inflammasome-dependent inflammation. Conclusions P2X7R of microglia in spinal cord mediates neuroinflammation by regulating NLRP3 inflammasome-dependent inflammation after spinal cord injury.
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