关键词: Bone marrow Cartilage Disease-modifying Injection Intra-articular Mesenchymal stromal cells (MSCs) Osteoarthritis Stem cells

Mesh : Animals Bone Marrow / pathology Osteoarthritis / therapy pathology Synovial Membrane / pathology Disease Models, Animal Injections, Intra-Articular Mesenchymal Stem Cell Transplantation / methods Osteoarthritis, Knee / therapy

来  源:   DOI:10.1007/s00167-023-07320-3   PDF(Pubmed)

Abstract:
OBJECTIVE: Aim of this systematic review was to determine if bone marrow-derived cell-based injectable therapies induce disease-modifying effects in joints affected by osteoarthritis (OA) in animal models.
METHODS: A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical animal studies comparing injectable bone marrow-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE\'s tool.
RESULTS: Fifty-three studies were included (1819 animals) with an increasing publication trend over time. Expanded cells were used in 48 studies, point-of-care products in 3 studies, and both approaches were investigated in 2 studies. Among the 47 studies presenting results on the disease-modifying effects, 40 studies (85%) reported better results with bone marrow-derived products compared to OA controls, with positive findings evident in 14 out of 20 studies (70%) in macroscopic assessment, in 30 out of 41 studies (73%) in histological assessment, and in 10 out of 13 studies (77%) in immunohistochemical evaluations. Clinical evaluations showed positive results in 7 studies out of 9 (78%), positive imaging results in 11 studies out of 17 (65%), and positive biomarker results in 5 studies out of 10 (50%). While 36 out of 46 studies (78%) reported positive results at the cartilage level, only 3 out of 10 studies (30%) could detect positive changes at the synovial level. The risk of bias was low in 42% of items, unclear in 50%, and high in 8%.
CONCLUSIONS: This systematic review of preclinical studies demonstrated that intra-articular injections of bone marrow-derived products can induce disease-modifying effects in the treatment of OA, slowing down the progression of cartilage damage with benefits at macroscopic, histological, and immunohistochemical levels. Positive results have been also observed in terms of clinical and imaging findings, as well as in the modulation of inflammatory and cartilage biomarkers, while poor effects have been described on the synovial membrane. These findings are important to understand the potential of bone marrow-derived products and to guide further research to optimise their use in the clinical practice.
METHODS: II.
摘要:
目的:本系统综述的目的是确定在动物模型中骨髓来源的基于细胞的可注射疗法是否在受骨关节炎(OA)影响的关节中诱导疾病缓解作用。
方法:对三个电子数据库(PubMed,WebofScience,Embase)根据PRISMA指南。对结果进行了综合研究,研究了临床前动物研究中的疾病改善作用,将可注射的骨髓衍生产品与OA对照或其他产品进行比较。不同的配方或注射间隔,以及与其他产品的结合。根据SYRCLE的工具评估偏倚风险。
结果:纳入了53项研究(1819只动物),随着时间的推移,其发表趋势不断增加。扩增的细胞用于48项研究,3项研究中的护理产品,两种方法在2项研究中进行了研究。在47项关于疾病改善效应的研究中,40项研究(85%)报告了与OA对照相比,骨髓衍生产品的结果更好,在宏观评估的20项研究中有14项(70%)得到了积极的结果,在41项组织学评估研究中的30项(73%)中,13项研究中有10项(77%)进行了免疫组织化学评估。临床评估显示9项研究中的7项(78%)结果为阳性,17项研究中有11项成像结果呈阳性(65%),10项研究中有5项(50%)的生物标志物结果呈阳性。46项研究中有36项(78%)在软骨水平上报告了阳性结果,10项研究中只有3项(30%)能检测到滑膜水平的阳性变化.在42%的项目中,偏倚的风险很低,50%不清楚,高达8%。
结论:这项对临床前研究的系统评价表明,关节内注射骨髓衍生产品可以在治疗OA中产生疾病缓解作用,减缓软骨损伤的进展,在宏观上有好处,组织学,和免疫组织化学水平。在临床和影像学发现方面也观察到了积极的结果,以及在炎症和软骨生物标志物的调节中,而对滑膜的影响较差。这些发现对于了解骨髓衍生产品的潜力并指导进一步的研究以优化其在临床实践中的使用非常重要。
方法:II.
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