Sajadi Simin, Khadembashiri Mohammad Amin, Raissi Gholamreza, Khadembashiri Mohamad Mehdi, Mansouri Korosh, Hadizadeh-Kharazi Homayoun, Joghataei Mohammad Taghi, Madani Seyed Pezhman, Forogh Bijan, Parsipour Sina
Department of Physical Medicine and Rehabilitation, Neuromusculoskeletal Research Center, School of Medicine, Firoozgar Hospital, Iran University of Medical Sciences, Behafarin Avenue, Tehran, 15934748711, Iran.
Student Research Committee, Tehran University of Medical Sciences, Tehran, Iran.
Stem Cell Res Ther. 2025 May 14;16(1):242. doi: 10.1186/s13287-025-04233-5.
Osteoarthritis (OA) is a degenerative joint disease that primarily affects older adults, characterized by cartilage degradation, synovitis, and osteophyte formation. Despite its prevalence, no medical treatment can reverse the joint cartilage degradation, leading many patients to undergo invasive procedures such as arthroplasty. Mesenchymal stem cells (MSCs), particularly those derived from adipose tissue, have emerged as a promising therapeutic approach due to their ability to differentiate into chondrocytes and potentially regenerate cartilage. While MSCs from bone marrow and umbilical cord have shown efficacy in treating OA, adipose-derived MSCs (ADMSC) are more accessible and cost-effective. This study aims to evaluate the safety and efficacy of allogeneic ADMSC in treating knee OA.
This triple-blind, interventional clinical trial included 20 patients with idiopathic knee OA, meeting the American College of Rheumatology (ACR) criteria. Patients were randomly assigned to receive an intra-articular injection of either 0.5 × 10 allogeneic ADMSC or saline (control group). Participants were evaluated for clinical signs of inflammation at baseline, and then at 2 weeks, 2 months, and 6 months post-injection using clinical assessments, the Visual Analogue Scale (VAS), Knee injury and Osteoarthritis Outcome Score (KOOS), range of motion (ROM), and Magnetic Resonance Arthrography (MRA).
The ADMSC group exhibited significant improvement in pain reduction as measured by VAS scores compared to the control group (P < 0.05). However, no significant differences were observed between the groups in ROM, and based on KOOS; quality of life, activity of daily living (ADL), recreation and sports activities, symptom and pain. Although there were no significant changes in ADL, recreation, and sports activities between groups, the ADMSC group showed significant improvements between several follow-up periods. Similar improvements were reported in the ADMSC group between several follow-ups' periods on other scales. Radiological outcomes showed a significant increase in cartilage thickness at specific locations (e.g., middle-lateral patella (P = 0.017), Tibial compartment lateral (P < 0.000)) in the ADMSC group after 6 months, demonstrating the regenerative potential of ADMSC in certain MRA sites. Multivariable analysis underlines the complexity of the interactions among treatment, time, and baseline level of variables. Although ADMSC treatment shows potential for some measures, its effects are not consistently significant for all measures.
Allogeneic ADMSC are safe and effective in reducing pain (based on VAS scale) and increasing cartilage thickness in knee OA patients. However, they do not significantly enhance quality of life or daily activity compared to placebo. Further research with larger sample sizes and longer follow-up periods is needed to confirm these findings and determine optimal dosing strategies.
Trial Registry Code: IRCT2016021123298N3, 20 February 2016. https://irct.behdasht.gov.ir/trial/19909.
骨关节炎（OA）是一种主要影响老年人的退行性关节疾病，其特征为软骨降解、滑膜炎和骨赘形成。尽管其发病率很高，但尚无药物治疗能够逆转关节软骨的降解，这导致许多患者接受诸如关节成形术等侵入性手术。间充质干细胞（MSCs），尤其是那些源自脂肪组织的间充质干细胞，因其能够分化为软骨细胞并可能再生软骨的能力，已成为一种有前景的治疗方法。虽然来自骨髓和脐带的间充质干细胞在治疗骨关节炎方面已显示出疗效，但脂肪来源的间充质干细胞（ADMSC）更容易获取且成本效益更高。本研究旨在评估同种异体ADMSC治疗膝骨关节炎的安全性和有效性。
这项三盲、干预性临床试验纳入了20例符合美国风湿病学会（ACR）标准的特发性膝骨关节炎患者。患者被随机分配接受关节腔内注射0.5×10的同种异体ADMSC或生理盐水（对照组）。在基线时以及注射后2周、2个月和6个月，使用临床评估、视觉模拟评分量表（VAS）、膝关节损伤和骨关节炎疗效评分（KOOS）、活动范围（ROM）以及磁共振关节造影（MRA）对参与者的炎症临床体征进行评估。
与对照组相比，ADMSC组在通过VAS评分测量的疼痛减轻方面表现出显著改善（P < 0.05）。然而，在ROM方面以及基于KOOS；生活质量、日常生活活动（ADL）、娱乐和体育活动、症状和疼痛方面，两组之间未观察到显著差异。尽管两组之间在ADL、娱乐和体育活动方面没有显著变化，但ADMSC组在几个随访期之间显示出显著改善。在其他量表上，ADMSC组在几个随访期之间也报告了类似的改善。放射学结果显示，6个月后ADMSC组特定部位（如髌骨中外侧（P = 0.017）、胫骨外侧间室（P < 0.000））的软骨厚度显著增加，这证明了ADMSC在某些MRA部位的再生潜力。多变量分析强调了治疗、时间和变量基线水平之间相互作用的复杂性。尽管ADMSC治疗在某些指标上显示出潜力，但其效果并非对所有指标都始终显著。
同种异体ADMSC在减轻膝骨关节炎患者的疼痛（基于VAS量表）和增加软骨厚度方面是安全有效的。然而，与安慰剂相比，它们并未显著提高生活质量或日常活动能力。需要进行更大样本量和更长随访期的进一步研究来证实这些发现并确定最佳给药策略。
试验注册号：IRCT2016021123298N3，2016年2月20日。https://irct.behdasht.gov.ir/trial/19909
