Department of Orthopaedic Surgery, Center for Joint Diseases, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea.
Department of Orthopaedic Surgery, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Am J Sports Med. 2023 Mar;51(3):837-848. doi: 10.1177/03635465211053893. Epub 2022 Jan 12.
Intra-articular injection of adipose-derived stem cells, which are divided into adipose-derived mesenchymal stem cells (ASCs) and adipose-derived stromal vascular fractions (ADSVFs), has been reported to be a viable treatment modality for knee osteoarthritis (OA); however, its efficacy remains limited.
This study aimed to provide comprehensive information about the efficacy and safety of intra-articular injections of autologous ASCs and ADSVFs without adjuvant treatment in patients with knee OA.
Meta-analysis; Level of evidence, 1.
A systematic search of the MEDLINE, Embase, Web of Science, and Cochrane Library databases was performed to identify randomized controlled trials (RCTs) that evaluated the efficacy and safety of intra-articular injections of autologous ASCs or ADSVFs without adjuvant treatments compared with placebo or hyaluronic acid in patients with knee OA. Clinically, the 100-mm visual analog scale for pain relief and the Western Ontario and McMaster Universities Osteoarthritis Index for functional improvement were implemented. Radiologically, cartilage status was assessed using magnetic resonance imaging (MRI). Procedure-related knee pain, swelling, and adverse events (AEs) were evaluated for safety. Additionally, we performed subgroup analyses comparing ASCs versus ADSVFs. Methodological quality was assessed using the modified Coleman Methodology Score (mCMS).
A total of 5 RCTs were included in this study. Based on the meta-analysis, ASCs or ADSVFs showed significantly better pain relief at 6 months ( = 7.62; < .0001) and 12 months ( = 7.21; < .0001) and functional improvement at 6 months ( = 4.13; < .0001) and 12 months ( = 3.79; = .0002), without a difference in procedure-related knee pain or swelling compared with controls. Although a meta-analysis with regard to cartilage improvements was not performed owing to heterogeneous MRI assessment, 3 studies reported significantly improved cartilage status after the injection. No serious AEs associated with ASCs or ADSVFs were reported. Subgroup analyses showed similar efficacy between ASC and ADSVF treatments. The median mCMS was 70 (range, 55-75).
For patients with knee OA, intra-articular injection of autologous ASCs or ADSVFs without adjuvant treatment showed remarkable clinical efficacy and safety at short-term follow-up. Some degree of efficacy has been shown for cartilage regeneration in knee OA, although the evidence remains limited. Further RCTs that directly compare ASCs and ADSVFs are needed.
关节内注射脂肪来源的干细胞，可分为脂肪来源的间充质干细胞（ASCs）和脂肪来源的基质血管部分（ADSVFs），已被报道为治疗膝骨关节炎（OA）的可行方法；然而，其疗效仍然有限。
本研究旨在提供关于关节内注射自体 ASCs 和 ADSVFs 治疗膝 OA 患者的疗效和安全性的综合信息，不使用辅助治疗。
荟萃分析；证据水平，1 级。
系统检索 MEDLINE、Embase、Web of Science 和 Cochrane 图书馆数据库，以确定评价关节内注射自体 ASCs 或 ADSVFs 治疗膝 OA 患者的疗效和安全性的随机对照试验（RCT），与安慰剂或透明质酸比较。临床方面，采用 100 毫米视觉模拟评分（VAS）评估疼痛缓解，采用西部安大略省和麦克马斯特大学骨关节炎指数（WOMAC）评估功能改善。影像学方面，采用磁共振成像（MRI）评估软骨状况。评估与操作相关的膝关节疼痛、肿胀和不良事件（AE）以评估安全性。此外，我们还进行了 ASC 与 ADSVF 比较的亚组分析。采用改良 Coleman 方法学评分（mCMS）评估方法学质量。
本研究共纳入 5 项 RCT。基于荟萃分析，ASCs 或 ADSVFs 在 6 个月（ = 7.62；<.0001）和 12 个月（ = 7.21；<.0001）时疼痛缓解明显更好，在 6 个月（ = 4.13；<.0001）和 12 个月（ = 3.79；=.0002）时功能改善明显更好，与对照组相比，与操作相关的膝关节疼痛或肿胀无差异。尽管由于 MRI 评估存在异质性，未进行关于软骨改善的荟萃分析，但 3 项研究报告了注射后软骨状况明显改善。未报告与 ASCs 或 ADSVFs 相关的严重不良事件。亚组分析显示 ASC 和 ADSVF 治疗的疗效相似。中值 mCMS 为 70（范围，55-75）。
对于膝骨关节炎患者，关节内注射自体 ASCs 或 ADSVFs 不联合辅助治疗在短期随访中显示出显著的临床疗效和安全性。在膝骨关节炎的软骨再生方面显示出一定程度的疗效，但证据仍然有限。需要进一步开展直接比较 ASCs 和 ADSVFs 的 RCT。
