Experimental Studies in Tendinopathy and The Effects of Mesenchymal Stem Cells on Healing: An Ovine Model

Abstract

Tendon injuries are a major problem in athletic horses and represent the most common form of musculoskeletal injury. Recurrent injury is common and re-injury rates of up to 53% have been demonstrated within 3 years. Historically, clinical treatments have limited efficacy; producing suboptimal results and not reducing re-injury risk. Stem cells have been injected into clinical and experimental equine superficial digital flexor tendon (SDFT) injuries with encouraging results. The aims of this thesis were to investigate the possible adverse effects that localised tendon injury could have on adjacent, regional tendons, as a potential cause of re-injury, and to determine the optimal time for implantation of mesenchymal stem cells following injury to enhance tendon healing. The effects of these interventions were assessed through biomechanical, histopathological and biomolecular analyses on an ovine model of tendinopathy. Focal surgical injury to the SDFT resulted in a mild tendinopathy within the deep digital flexor tendon eight weeks after the initial injury. These changes appeared to resolve over time, with improvements in histological and gene expression parameters, with no significant biomechanical effects observed at 12 and 26 weeks. Complete transection of the extensor tendons did not affect the health and function of either flexor tendon at eight weeks. Treatment of focal surgical injury of the SDFT with a single injection of allogeneic bone marrow-derived mesenchymal stem cells at two weeks resulted in improvements in histological, gene expression and biomechanical parameters at 26 weeks. Alternatively, treatment with mesenchymal stem cells at eight weeks showed no significant differences compared with operated controls. The results of this study suggest that early therapy with stem cells following injury is likely to enhance healing and provide a better outcome.