Novel treatments in equine medicine: differences in the expression of inflammatory molecules

In equine practice, lameness due to musculoskeletal disease is the most common diagnosis, with ligament and tendon injuries resulting as the most frequent lesions. These kinds of injuries have a significant impact on the horse’s athletic performance as well as their quality of life; furthermore, the economic cost for the required treatments is very high. Currently, the most common therapy is surgery, that is usually associated to stall rest and pharmacological management of the inflammatory stage that follows the lesion. These therapies aim to repair the lesion, but the newformed cellular material does not have the same biological and biomechanical properties of the native tissue. In fact, tendons and ligaments are poorly vascularized tissues consisting of few cells lying in abundant extracellular matrix, the healing process is slow and leads to the formation of scar tissue, and often, to high reinjury rates that can reach over the 80% of the cases. The aim of regenerative medicine is not only to provide wound healing, but to repair damaged tissues too, leading to the restoration of the normal function of the injured tissue. In the case of tendon and ligament lesions, regenerative medicine aims to restore both the structure of collagen fibers and their biomechanical proprieties, so that after the lesion has healed, tendon’s structure and function is the most possible like the original tissue; this achievement should allow the horse to get back to the same activities it was used to and, moreover, to the same performance level with minimum risks of reinjury. In this study, a double-injection of adipose derived mesenchymal stem cells associated to platelet rich plasma was performed on two horses affected of tendonitis of the superficial digital flexor tendon of one forelimb. Clinical assessments were performed every 2 weeks starting from the day of the first injection; general condition, pain, heat and swelling at the site of the injury, grade of lameness and the horse keeper’s evaluation were the considered parameters. Ultrasonographic evaluations of the metacarpal region of both forelimbs were performed by means of longitudinal and transverse scans. The obtained images were evaluated and scored for i) the lesion echogenicity and ii) the lesion longitudinal fiber alignment; the contralateral healthy limb was used as comparison. Horse plasma was also analyzed in both horses at baseline, one week and two weeks post-injection, and in subject n°2 also one week prior to treatment and one month after treatment, in order to assess different oxidative stress molecules’ levels: total protein, advanced oxidation protein products, carbonyl group and malondialdehyde. Two interleukins important in the inflammatory process were also estimated: interleukin 1 and interleukin 10. Platelet derived growth factor, insulin-like growth factor 1 and transforming growth factor β1 values were also determined. The results of this study suggest a beneficial effect of the performed combined treatment that demonstrated to be safe and effective; importantly, no adverse reactions were observed, as confirmed my biochemical parameters, and the horses were able to get back to competition. These evidences might therefore encourage the combined application of mesenchymal stem cells and platelet rich plasma for the treatment of tendon injuries in equine clinical practice.