Abstract
Background: Tendon injuries are very common in horses and jeopardize the athletic performance, and due to the high risk of reinjury may lead to early retirement. The use of mesenchymal stem cells for the treatment of equine tendon disease is widely investigated because of their regenerative potential. The objective of this study is to investigate the safety and efficacy of equine allogeneic tenogenic primed mesenchymal stem cells (tpMSCs) for the management of tendinitis in horses.Methods: A core lesion was surgically induced in the superficial digital flexor tendon of both forelimbs of eight horses. After 7 days, one forelimb was treated with tpMSCs, while the contralateral forelimb served as an intra-individual control and was treated with saline. A prescribed exercise program was started. All horses underwent a daily clinical evaluation throughout the entire study period of 112 days. Blood samples were taken at different time points for hematological and biochemical analysis. Tendon assessment, lameness examination, ultrasound assessment and ultrasound tissue characterization (UTC) were performed at regular time intervals. At the end of the study period, the superficial digital flexor tendons were evaluated macroscopically and histologically.Results: No suspected or serious adverse events occurred during the entire study period. There was no difference in local effects including heat and pain to pressure between a single intralesional injection of allogeneic tpMSCs and a single intralesional injection with saline. A transient moderate local swelling was noted in the tpMSC treated limbs, which dissipated by day 11. Starting at a different time point depending on the parameter, a significant improvement was observed in the tpMSC treated limbs compared to the placebo for echogenicity score, fiber alignment score, anterior-posterior thickness of the tendon and echo type by UTC assessment. Immunohistochemistry 112 days post-injection revealed that the amount of collagen type I and Von Willebrand factor were significantly higher in the tendon tissue of the tpMSC group, while the amount of collagen type III and smooth muscle actin was significantly lower.Conclusion: Equine allogeneic tenogenic primed mesenchymal stem cells were shown to be well-tolerated and may be effective for the management of tendon injuries.
Highlights
Tendon injuries are very common in both human [1, 2] and equine athletes [3, 4], and often result in reinjury or early retirement [5]
Beerts et al [29] reported that 85.7% of horses with a naturally occurring lesion in the superficial digital flexor tendon (SDFT) returned to their previous performance level after treatment with tenogenic primed mesenchymal stem cells (tpMSCs) in combination with platelet rich plasma (PRP) in a 2-year follow-up study. These findings indicate that the use of tpMSCs in combination with PRP is promising for future applications
Due to the study design each horse received the control product (CP) in one of its forelimbs, whereas, the contralateral limb in each horse was treated with the investigational product (IVP)
Summary
Tendon injuries are very common in both human [1, 2] and equine athletes [3, 4], and often result in reinjury or early retirement [5]. Healthy tendon tissue is mainly composed of type I collagen, contributing to a remarkable tensile strength and elasticity. The smaller and less organized fibrils of collagen type III result in loss of original tensile strength and elasticity [13, 14]. The repair tissue never reaches the tensile characteristics of healthy tendon, resulting in the formation of rigid scar tissue with increased risk of tendon reinjury [12, 15]. Tendon injuries are very common in horses and jeopardize the athletic performance, and due to the high risk of reinjury may lead to early retirement. The objective of this study is to investigate the safety and efficacy of equine allogeneic tenogenic primed mesenchymal stem cells (tpMSCs) for the management of tendinitis in horses
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