The Evaluation of Equine Allogeneic Tenogenic Primed Mesenchymal Stem Cells in a Surgically Induced Superficial Digital Flexor Tendon Lesion Model

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.

Cellular and Humoral Immunogenicity Investigation of Single and Repeated Allogeneic Tenogenic Primed Mesenchymal Stem Cell Treatments in Horses Suffering From Tendon Injuries

“…Based on current results, it remains unclear whether this could be related to the presence of a naturally occurring equine sarcoid in one sero-converting horse or if it is an individual non-specific immune response against one or several different (xeno)antigens. Despite the occurrence of the non-specific immune response in one horse, a previous study performed by our group including these horses revealed no clinical abnormalities and promising results of the tpMSC treatment ( 46 ). Owens et al, reported an anti-BM-MSC antibody response in 37% of the horses receiving an allogeneic treatment ( 15 ).…”

“…Furthermore, in clinical studies, the allogeneic use of MSCs has been described for single ( 12 , 23 , 46 ) and repeated ( 24 , 25 ) treatment of horses suffering from tendon injuries without evidence of any local immunological reactions (absence of heat, swelling, pain or lameness) after intralesional injection. On the other hand, a higher number of circulating CD8 T-cells after repeated intravenous injection of equine allogeneic MSCs has been reported ( 56 , 57 ).…”

“…For the first study, eight warmblood horses (four geldings and four mares; age ranged between 3 and 12 years) with a surgically induced superficial digital flexor tendon (SDFT) core lesion enrolled in a previous study performed by our group received a single intralesional treatment with a proprietary formulation of 3 × 10 6 equine allogeneic tenogenic primed mesenchymal stem cells (tpMSCs) ( 46 ). To assess the cellular immune response, 9 mL of whole blood was collected aseptically from the vena jugularis into sterile ethylenediaminetetraacetic acid (EDTA) tubes before treatment and 16 weeks after treatment.…”

Case Report: Repeated Intralesional Injections of Autologous Mesenchymal Stem Cells Combined With Platelet-Rich Plasma for Superficial Digital Flexor Tendon Healing in a Show Jumping Horse

“…For each assessment, a complete examination of the SDFT was conducted by means of longitudinal and transverse scans. The obtained images were evaluated and scored (from 0 to 3) at each examination for two parameters as previously described (24,39): lesion echogenicity and lesion longitudinal fiber alignment (FA). Criteria for scoring are listed in Table 1.…”

“…Mesenchymal stem cells (MSCs) derived from multiple sources, as bone marrow (BM-MSCs), adipose tissue (AD-MSCs), or peripheral blood (PB-MSCs), have proved their efficacy in improving tendon healing in horses thus reducing the reoccurrence rate of injury, mainly because of their paracrine activity (21)(22)(23)(24). Different route of administration of MSCs, including intralesional injection, have demonstrated to be a safe and effective practice to treat tendon injury in equine medicine (25,26).…”