Department of Orthopaedic, University Clinic Aachen, RWTH Aachen University Clinic, Pauwelsstraße 30, 52074, Aachen, Germany.
Department of Thoracic Surgery, University Clinic Aachen, RWTH Aachen University Clinic, Aachen, Germany.
Arch Orthop Trauma Surg. 2020 Jul;140(7):853-868. doi: 10.1007/s00402-019-03267-8. Epub 2019 Aug 27.
According to the World Health organization (WHO), more than 10% in people older than 60 years suffer from osteoarthritis (OA). Over the last years, there has been an increased interest around regenerative medicine, especially regarding stem cell treatments and related applications. We hypothesize that stem cell therapies can represent a feasible option for idiopathic knee OA, delaying or even avoiding the joint replacement. To emphasize the potential of percutaneous injections of mesenchymal stem cells for knee OA, a comprehensive systematic review of the literature was conducted.
Two independent authors (FM, GC) performed the literature search. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The main databases were accessed: Pubmed, Embase, Google Scholar, Cochrane Systematic Reviews, Scopus, AMED. For this systematic review, all articles treating percutaneous injections of mesenchymal stem cells for knee OA were considered. Because of the rapid advancements promoted by the scientific progress on stem cell expansion and processing, only articles published within the last five years were included. Solely articles reporting the outcomes of interest across 6- and 12-month follow-up were recruited for eligibility. We included only studies reporting quantitative data under the outcomes of interest. We referred for the quality assessment to the Coleman Methodology Score (CMS). The statistical analysis was performed with Review Manager Software 5.3 (The Nordic Cochrane Centre, Copenhagen).
A total of 18 studies were enrolled in the present study, comprising 1069 treated knees. The mean age of the samples was 57.39 ± 7.37 years. 72% of the included studies harvested the stem cells from the iliac crest (bone marrow-derived MSCs), the remaining 28% from the adipose tissue (adipose-derived MSCs). The mean visual analogic scale improved from 18.37 to 30.98 and 36.91 at 6- and 12-month follow-up, respectively. The mean WOMAC score improved from 25.66 to 25.23 and 15.60 at 6- and 12-month follow-up, respectively. The mean walking distance improved from 71.90 to 152.22 and 316.72 at 6- and 12-month follow-up, respectively. The mean Lequesne scale improved from 33.76 to 12.90 at 12-month follow-up. The KOOS score improved from 41.07 to 8.47% and 18.94 at 6- and 12-month follow-up. All the KOOS subscales improved significantly from the baseline. A total of 136 (12.7%) local complications were detected.
According to the current evidences and the main findings of this systematic review, we reported that MSC infiltrations for knee OA can represent a feasible option, leading to an overall remarkable improvement of all clinical and functional considered outcomes, regardless of the cell source. Patients treated at earlier-degeneration stages reported statistically significant greater outcomes. The pain and function scores were improved considerably, thus, leading to a significant improvement of patient participation in recreational activities and quality of life.
根据世界卫生组织（WHO）的数据，超过 60 岁的人群中有 10%以上患有骨关节炎（OA）。近年来，再生医学受到了越来越多的关注，尤其是干细胞治疗及其相关应用。我们假设干细胞疗法可以作为特发性膝骨关节炎的可行选择，延缓甚至避免关节置换。为了强调经皮注射间充质干细胞治疗膝骨关节炎的潜力，我们对文献进行了全面的系统综述。
两名独立作者（FM、GC）进行了文献检索。本研究按照系统评价和荟萃分析的首选报告项目（PRISMA）进行。主要数据库包括：PubMed、Embase、Google Scholar、Cochrane 系统评价、Scopus、AMED。本系统评价纳入了所有治疗膝骨关节炎经皮注射间充质干细胞的文章。由于干细胞扩增和处理方面的科学进步迅速，仅纳入了过去五年内发表的文章。仅纳入了报告 6 个月和 12 个月随访时感兴趣结局的文章进行合格性评估。我们仅纳入了报告感兴趣结局的定量数据的研究。我们参考 Coleman 方法学评分（CMS）进行质量评估。统计分析使用 Review Manager Software 5.3（北欧 Cochrane 中心，哥本哈根）进行。
本研究共纳入了 18 项研究，共纳入了 1069 例治疗膝关节。样本的平均年龄为 57.39±7.37 岁。72%的纳入研究从髂嵴（骨髓来源的间充质干细胞）中提取干细胞，其余 28%从脂肪组织（脂肪来源的间充质干细胞）中提取。6 个月和 12 个月随访时，平均视觉模拟评分分别从 18.37 改善至 30.98 和 36.91。6 个月和 12 个月随访时，平均 WOMAC 评分分别从 25.66 改善至 25.23 和 15.60。6 个月和 12 个月随访时，平均步行距离分别从 71.90 改善至 152.22 和 316.72。12 个月随访时，平均 Lequesne 评分从 33.76 改善至 12.90。6 个月和 12 个月随访时，KOOS 评分分别从 41.07 改善至 8.47%和 18.94。所有 KOOS 亚量表均从基线显著改善。共检测到 136 例（12.7%）局部并发症。
根据目前的证据和本系统评价的主要发现，我们报告称，膝骨关节炎的 MSC 浸润可以作为一种可行的选择，可导致所有考虑的临床和功能结局的整体显著改善，而与细胞来源无关。在早期退变阶段接受治疗的患者报告的结果具有统计学意义上的显著改善。疼痛和功能评分有了显著改善，从而显著提高了患者参与娱乐活动和生活质量的能力。
