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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 6 , range 5-19 × 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., (© 2024. The Author(s).)

Tendinopathy remains one of the most common musculoskeletal disorders affecting both human and equine athletes and presents a considerable therapeutic challenge. The following workshop report comes from the third Dorothy Havemeyer Symposium of Tendinopathy which provided a unique overview of our current understanding of both the basic science and the clinical challenges for diagnosing and treating tendinopathy in both species. Pathologically, tendon demonstrates alterations in both cellular, molecular, structural, and biomechanical features, leading to a spectrum of pathological endotypes. To develop novel interventions to manage, treat or prevent tendinopathies it is vital to understand the underlying mechanisms that lead to both tendon failure, and also regeneration and resolution of inflammation. The horse shows analogous pathology with both human Achilles tendinopathy (superficial digital flexor tendon) and intrathecal rotator cuff tears (deep digital flexor tendon tears) enabling scientists and clinicians from both medical and veterinary fields to work jointly on matching naturally occurring disease models. The experience in human medicine on the design, conduct, and impact of clinical trials has much to inform clinical trials in horses. There is a need to design appropriate studies to address clear questions, socialize the study to achieve good enrollment, and consider the significance and impact of the clinical question as well as the cost of addressing it. Because economics is often a limitation in equine medicine the use of observational studies, and specifically registries, should be given careful consideration., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)