Much of the exploration into new treatment options for tendon injuries in animals has taken place in the horse. The Royal Veterinary College was the setting of the first use of stem cell therapy for tendon injuries in horses, and the technique has also been used for equine joint disease.

Much of the development has involved the careful assessment of clinical information, rather than using experimentally induced injuries in experimental animals.

Stem cell based treatments are valuable to equine vets and their patients because established treatments (e.g. surgery, ice application, bandage, box rest and controlled exercise, use of corticosteroids and other substances) have not improved the outcome. This is particularly the case for tendon degenerative disorders which do not regenerate but instead heal with scar tissue such that functionality is not fully restored.

Applications and benefits

Stem cell based techniques used in horses are being translated in pilot studies into treatment of human tendon injuries, where injuries associated with athletic activity and ageing frequently occur in both species and thus have close similarities.

vet performing ultrasound scan on horse's leg
Ultrasound of flexor tendons to detect tendon injury and monitor repair

In comparison with established tendon treatments, stem cell based treatments have shown improved outcomes, by halving the re-injury rate in both racehorses and sports horses compared to conventional management. 

These studies have been performed on a sufficiently large group of clinical cases presenting at equine practices nationally and followed for three years after treatment in order to compare with other treatments with adequate statistical power. 

The injury itself only causes pain and lameness for a short period, but when the injury is severe often results in euthanasia because of the poor prognosis for a successful return to performance.

Therefore, in a small number of cases (14 horses), with full consent from owners, horses that were already destined for euthanasia due to a career-ending tendon injury were recruited for stem cell treatment in a much more controlled study conducted under the Animals Scientific Procedures Act (ASPA).

These horses were divided into two groups, where one group received stem cells in their inured tendon and the other group received only saline (control group) in their injured tendon. All horses underwent the same rehabilitation protocol as used clinically for six months at which point they were humanely euthanised and their tendons analysed in the laboratory.

As with any ASPA study, every care was taken to ensure the welfare of the horses recruited.

This experimental controlled study has provided invaluable information on the quality of the tissue of the restored tendon compared to tendons that did not receive stem cell treatment and really adds significant weight to the clinical field observations that this treatment is effective in improving the quality of tendon repair.  

Thus, we can justifiably state that cell therapy produces a better quality repair most likely by the modulation of repair rather than being truly regenerative. Although stem cell based treatments are safe and efficacious in current analysis of clinical data, full proof would require large numbers treated in a randomised controlled trial, a difficult undertaking in essentially private medicine where the owner determines the choice of treatment.

Advances

microscope view of stem cells
Horse bone marrow mesenchymal stem cells in culture. The cells have been tagged with a green fluorescent antibody to show the expression of α2-integrin, a cell membrane protein. The nuclei of the cells are stained with a red dye

Further advances in stem cell technology to improve efficacy continue to be made. As well as evidence of success with equine patients, positive effects with small animals and non-equine large animals have been reported.

The use of mesenchymal stem cells (MSCs) in veterinary in orthopaedic practice has recently and rapidly acquired an important role. Therapies based on the use of MSCs for the treatment of acute injuries, as well as chronic inflammatory disorders, are gradually becoming clinically routine. These cells have demonstrated intriguing therapeutic potentialities (i.e. inflammation control, tissue regeneration and pathological scar prevention), that have been taken into consideration for use in both human and veterinary medicine.

Commercially available cell preparations are either minimally-manipulated stem cells or enriched stem cell products. Minimally-manipulated stem cell preparations may be  whole bone marrow, bone marrow nucleated cell fraction (BMAC - Bone marrow aspirate concentrate), or cell preparations made from fat (without undergoing further growth and expansion in numbers in the laboratory). Enriched stem cell products may be MSCs derived from bone marrow, fat tissue or umbilical cord blood that have been expanded in cell numbers in the laboratory.

Experience at The Royal Veterinary College suggests that the preparation process has a greater influence on the nature of the product than tissue source does, although there is currently no data comparing different products.

Ramifications for other species

The equine population is estimated to be about 800,000 in the UK. Tendon over-strain injuries are the most common orthopaedic injury in all equine disciplines and 25% of National Hunt horses in training have evidence of superficial digital flexor tendinopathy. The market size for stem cell therapy in horses is therefore considerable; however this is potentially greater for companion animals where the total population of dogs and cats is tenfold higher (about nine million in the UK). Supraspinatus tendinopathy in dogs is common and trials show positive outcomes in the US. The prevalence of hip and elbow osteoarthritis arthritis is 6.6% increasing to >10% in some purebred dogs and this is a potential new area for development of the treatment.

Stem cell based treatments for joints

The value of stem cell therapy for joints appears to be more limited than in tendon injuries. This is because there is limited adherence to cartilage. However, cells engrafted into the synovium and other soft tissues of the joint may still be able to modulate inflammation and repair which would significantly contribute to management of the disease and patient mobility and comfort. The treatment may be more appropriate for intrasynovial soft tissue lesions such as meniscal tears.

Tendinopathy

This video shows work inspired by research at the RVC and won first prize at the Orthopaedic Research Society (ORS) Media Outreach Awards.

The video was produced by Jan Barfoot (MRC Centre for Regenerative Medicine in Edinburgh - www.crm.ed.ac.uk) and Ryan Lewis (ScideLight - www.scidelight.com).

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