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., …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