Division of Surgery, UCL Institute of Orthopaedics & Musculoskeletal Science, Royal Free Hospital, 9th Floor (East), 2QG, 10 Pond St, London, NW3 2PS, UK.
Department of Research and Innovation, Royal National Orthopaedic Hospital (RNOH), Brockley Hill, Stanmore, Middlesex, UK.
Sci Rep. 2024 May 19;14(1):11421. doi: 10.1038/s41598-024-61399-3.
Achilles tendinopathy is a disabling condition that affects more than 50% of runners. Pre-clinical studies in a large animal model of naturally-occurring tendinopathy similar to human Achilles tendinopathy has shown benefits of autologous bone marrow-derived mesenchymal stem cell (MSC) implantation. However, MSCs are advanced therapies medicinal products (ATMPs), with strict regulatory requirements. Guided by the regulator we carried out a first in man study to assess the safety and efficacy of autologous MSC injection in human patients with non-insertional Achilles tendinopathy. Ten patients, mean age 47 with mid-portion Achilles tendon pain and swelling for more than 6 months, underwent autologous cultured cell injections (median 12.2 × 10, range 5-19 × 10 cells) into their Achilles tendon. At 24 weeks follow-up, no serious adverse reactions or important medical events were observed. MOXFQ, EQ-5D-5L, and VISA-A scores improved clinically at 12 and 24 weeks. VAS pain improved increasingly at 6, 12 and 24 weeks. MOXFQ Pain and VISA-A Scores improved > 12 points from baseline to 24 weeks in 8 patients. Maximum anteroposterior tendon thickness as measured by greyscale US decreased by mean 0.8 mm at 24 weeks. This phase IIa study demonstrated the safety of autologous MSC injection for non-insertional Achilles tendinopathy and provides proof-of-concept of the technique in patients, all of whom had previously failed conservative treatments for chronic disease and leads the way for a larger randomised controlled trial.
跟腱病是一种使人丧失能力的疾病，影响 50%以上的跑步者。在类似于人类跟腱病的自然发生的跟腱病大动物模型的临床前研究表明，自体骨髓间充质干细胞（MSC）植入具有益处。然而，MSC 是先进的治疗性药物产品（ATMP），具有严格的监管要求。在监管机构的指导下，我们进行了首例人体研究，以评估自体 MSC 注射治疗非插入性跟腱病患者的安全性和有效性。10 名患者，平均年龄 47 岁，中段跟腱疼痛和肿胀超过 6 个月，接受了自体培养细胞注射（中位数 12.2×10，范围 5-19×10 个细胞）到他们的跟腱。在 24 周随访时，未观察到严重不良反应或重要医疗事件。MOXFQ、EQ-5D-5L 和 VISA-A 评分在 12 和 24 周时临床改善。VAS 疼痛在 6、12 和 24 周时逐渐改善。8 名患者从基线到 24 周时 MOXFQ 疼痛和 VISA-A 评分改善超过 12 分。最大前后肌腱厚度（通过灰阶超声测量）在 24 周时平均减少 0.8 毫米。这项 IIa 期研究证明了自体 MSC 注射治疗非插入性跟腱病的安全性，并为患者提供了该技术的概念验证，所有患者先前均因慢性疾病而未能接受保守治疗，为更大规模的随机对照试验铺平了道路。
