Chahla Jorge, Piuzzi Nicolas S, Mitchell Justin J, Dean Chase S, Pascual-Garrido Cecilia, LaPrade Robert F, Muschler George F
Steadman Philippon Research lnstitute, Vail, Colorado
Institute of Orthopedics, "Carlos E. Ottolenghi" Italian Hospital of Buenos Aires, Buenos Aires, Argentina
J Bone Joint Surg Am. 2016 Sep 21;98(18):1511-21. doi: 10.2106/JBJS.15.01495.
Intra-articular cellular therapy injections constitute an appealing strategy that may modify the intra-articular milieu or regenerate cartilage in the settings of osteoarthritis and focal cartilage defects. However, little consensus exists regarding the indications for cellular therapies, optimal cell sources, methods of preparation and delivery, or means by which outcomes should be reported.
We present a systematic review of the current literature regarding the safety and efficacy of cellular therapy delivered by intra-articular injection in the knee that provided a Level of Evidence of III or higher. A total of 420 papers were screened. Methodological quality was assessed using a modified Coleman methodology score.
Only 6 studies (4 Level II and 2 Level III) met the criteria to be included in this review; 3 studies were on treatment of osteoarthritis and 3 were on treatment of focal cartilage defects. These included 4 randomized controlled studies without blinding, 1 prospective cohort study, and 1 retrospective therapeutic case-control study. The studies varied widely with respect to cell sources, cell characterization, adjuvant therapies, and assessment of outcomes. Outcome was reported in a total of 300 knees (124 in the osteoarthritis studies and 176 in the cartilage defect studies). Mean follow-up was 21.0 months (range, 12 to 36 months). All studies reported improved outcomes with intra-articular cellular therapy and no major adverse events. The mean modified Coleman methodology score was 59.1 ± 16 (range, 32 to 82).
The studies of intra-articular cellular therapy injections for osteoarthritis and focal cartilage defects in the human knee suggested positive results with respect to clinical improvement and safety. However, the improvement was modest and a placebo effect cannot be disregarded. The overall quality of the literature was poor, and the methodological quality was fair, even among Level-II and III studies. Effective clinical assessment and optimization of injection therapies will demand greater attention to study methodology, including blinding; standardized quantitative methods for cell harvesting, processing, characterization, and delivery; and standardized reporting of clinical and structural outcomes.
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
关节内细胞治疗注射是一种有吸引力的策略，可能会改变骨关节炎和局限性软骨缺损情况下的关节内环境或使软骨再生。然而，关于细胞治疗的适应症、最佳细胞来源、制备和递送方法或报告结果的方式，几乎没有达成共识。
我们对当前关于膝关节内注射细胞治疗的安全性和有效性的文献进行了系统评价，这些文献提供了III级或更高的证据水平。共筛选了420篇论文。使用改良的科尔曼方法评分评估方法学质量。
只有6项研究（4项II级和2项III级）符合纳入本综述的标准；3项研究是关于骨关节炎的治疗，3项是关于局限性软骨缺损的治疗。其中包括4项非盲法随机对照研究、1项前瞻性队列研究和1项回顾性治疗病例对照研究。这些研究在细胞来源、细胞特征、辅助治疗和结果评估方面差异很大。总共300个膝关节报告了结果（骨关节炎研究中124个，软骨缺损研究中176个）。平均随访时间为21.0个月（范围为12至36个月）。所有研究均报告关节内细胞治疗的结果有所改善，且无重大不良事件。改良科尔曼方法评分的平均值为59.1±16（范围为32至82）。
关于膝关节骨关节炎和局限性软骨缺损的关节内细胞治疗注射的研究表明，在临床改善和安全性方面有积极结果。然而，改善程度不大，不能忽视安慰剂效应。文献的整体质量较差，即使在II级和III级研究中，方法学质量也一般。有效的临床评估和注射治疗的优化将需要更加关注研究方法，包括盲法；细胞采集、处理、特征化和递送的标准化定量方法；以及临床和结构结果的标准化报告。
治疗性III级。有关证据水平的完整描述，请参阅作者指南。
