Autologous bone marrow derived mesenchymal stem cells are safe for the treatment of Achilles tendinopathy

Goldberg, AJ; Masci, L; O'Donnell, P; Green, R; Brooking, D; Bassett, P; Lowdell, MW; Smith, RKW

Abstract

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 x 10(6), range 5-19 x 10(6) 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.

Citation

Goldberg, A., Masci, L., O'Donnell, P., Green, R., Brooking, D., Bassett, P., Lowdell, M., & Smith, R. (2024). Autologous bone marrow derived mesenchymal stem cells are safe for the treatment of Achilles tendinopathy. Scientific Reports, 14(1), https://doi.org/10.1038/s41598-024-61399-3

• Journal Article Type: Article
• Acceptance Date: May 6, 2024
• Online Publication Date: May 19, 2024
• Publication Date: 2024
• Deposit Date: Jun 3, 2024
• Publicly Available Date: Jun 3, 2024
• Print ISSN: 2045-2322
• Electronic ISSN: 2045-2322
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 1
• DOI: https://doi.org/10.1038/s41598-024-61399-3
• Keywords: ULTRASONOGRAPHIC TISSUE CHARACTERIZATION; DIGITAL FLEXOR TENDONS; ROTATOR CUFF REPAIR; PAIN SCORE; VISA-A; QUESTIONNAIRE; OUTCOMES; QUANTIFICATION; DIFFERENCE; SEVERITY