| Background and objective:Knee osteoarthritis is a chronic progressive disease,which is characterized by the disintegration of joint matrix and destruction of cartilage,and has become a highly crippling disease.In the past,palliative treatment was mostly used,including drug therapy,physiotherapy or exercise,which could only relieve clinical symptoms and could not reverse and repair the damaged articular cartilage,so most patients had joint pain and deformities,which greatly affected the quality of life of patients.Unfortunately,in the current guidelines for the prevention and treatment of osteoarthritis,there is no radical treatment for osteoarthritis,and comprehensive and multimodal treatment is still the main method.Because of the diversity of proliferation and differentiation,mesenchymal stem cell(MSCs)has a good application prospect in cartilage repair,stroke,cardiomyocyte regeneration and so on.At present,there are many studies on intra-articular injection of mesenchymal stem cells in the treatment of knee osteoarthritis,clinical trial design is different,and there is still a lack of exact evidence of its efficacy and safety.Therefore,on the basis of evidence-based medicine,this study included high-quality randomized controlled trials and meta-analyzed the efficacy and safety of related studies to explore the clinical efficacy and safety of mesenchymal stem cells in the treatment of knee osteoarthritis.Methods:All the literatures related to the treatment of knee osteoarthritis by intra-articular injection of mesenchymal stem cells in Pubmed,Embase,Cochrane and other databases before July 31,2020 were searched.Through the specific inclusion and exclusion criteria,the relevant data were collected and analyzed by Meta.Results:Twelve randomized controlled trials(RCTs)were included with visual analogue scale(VAS),osteoarthritis index of University of Western Ontario and McMaster University(WOMAC)and whole organ magnetic resonance imaging score(WORMS)as the main outcome indicators.Six months after mesenchymal stem cell treatment,the comprehensive weighted effect values of VAS and WOMAC were[MD,-16.03;95%CI(-19.39,-12.67);P<0.00001]and[SMD,-0.78;95%CI(-1.24,-0.32);P=0.0009].The comprehensive weighted effects of VAS and WOMAC in 12 months after MSCs treatment were[MD,-15.10;95%CI(-21.00,-9.20);P<0.00001]and[SMD,-0.70;95%CI(-0.95,-0.45);P<0.00001].The results showed that the difference of mesenchymal stem cells after treatment was statistically significant.However,there was no significant difference in VAS score at 24 months(p=0.09).There was also no statistical significance in WORMS score(p=0.65).In addition,the subgroup analysis results show that the cell type and dose of MSCs is not a heterogeneous source of treatment differences,MSCs to treat knee osteoarthritis may rely mainly on its paracrine effect.A safety evaluation of mesenchymal stem cells for the treatment of the knee joint showed similar adverse reactions compared to the control group,suggesting that intraarticular injection of mesenchymal stem cells is safe(p=0.18).Conclusions:Intra-articular injection of MSCs can relieve pain and improve the function of knee osteoarthritis in the short term,but there is no evidence of long-term effect.In addition,no strong evidence has been found to support intra-articular injection of mesenchymal stem cells to promote cartilage repair.Therefore,the use of mesenchymal stem cells in the treatment of osteoarthritis of the knee should be treated with caution. |
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