The Royal Veterinary College pioneered the use of stem cell therapy for tendon injuries in horses. This therapy has been particular useful for advancing treatment for “core” injuries that are located within the body of the tendon.
However, injuries also occur to tendons that are contained within a synovial sheath which is filled with synovial fluid. This anatomic arrangement helps the tendon to glide smoothly where it runs over a bony prominence. Injuries in this location commonly occur on the surface of the tendon which therefore exposes the inner body of the tendon with the outer synovial fluid environment, which we have shown to be a toxic mix for the tendon cells. These types of tendon injuries are a extremely common orthopaedic condition in humans and those domestic mammals that suffer naturally-occurring tendon injury, such as horses and dogs, where they do not heal and are particularly problematic to treat.
In humans, intrasynovial tendons in the shoulder help to move and rotate the arm. Injuries to these tendons are the third most common musculoskeletal complaint and pose a significant socioeconomic and treatment challenge. Estimates suggest that rotator cuff tears and ruptures affect 5-30% of adults and 40-50% of patients in the UK consult their general practitioners for shoulder pain. In addition to pain, rotator cuff tears can severely inhibit arm movement and can impair the ability to work or perform household tasks and result in increased time off from work.
In an attempt to treat intrasynovial injuries we performed a small proof-of-concept clinical trial with stem cells in horses that had naturally suffered such injuries. The treatment failed to heal the injury and similar negative findings have been reported in human rotator cuff injuries treated with stem cells. The treatment of intrasynovial injuries poses a special challenge for the development of novel therapies which is best met with an animal model with functional and pathological similarities to man.
Applications and benefits
In a study conducted under the Animals Scientific Procedures Act (ASPA) we have used a novel sheep model with a lesion in the forelimb (similar location to the horse). This mimics the mechanical and synovial environment of the rotator cuff in human patients although in an anatomically distinct location. We have used this model to study in detail the effects of mesenchymal stem cells administered intrasynovially. The lesion causes minimal inflammation and pain and the animals do not suffer from lameness. Unlike other laboratory animal models of tendon injury, this model mimics the failed tendon healing seen clinically but the intrasynovially administration of bone marrow-derived mesenchymal stem cells did not improve healing. However, the results from this model have been invaluable in understanding the fate and distribution of the injected stem cells within the tendon synovial sheath and have helped in the development of the next phase of treatment strategies. In a collaboration with tendon surgeons from human medicine we have applied a novel engineered material to suture or “patch” the lesion in our model. The engineered material in either form induced the closure of the lesion, something that is rarely observed in injuries in the horse or human patients with alternative (mainly surgical) treatments. Although the healed lesion does not repair into original tissue, nevertheless these results are exciting, novel and provide the opportunity to further refine the therapy.
Advances and clinical applications
The proof-of-concept study in the model has further provided critical safety data on the engineered material and paved the way for approval of a trial in human patients suffering from rotator cuff tears. If the tears heal, it could improve shoulder mobility and likely reduce pain. It similarly opens an opportunity to trial the therapy in horses, including novel approaches of modifying the engineered material applied in conjunction with stem cells.