Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon

Reasons for performing study: Mesenchymal stem (progenitor; stromal) cell (MSC) therapy has gained popularity for the treatment of equine tendon injuries but without reports of long‐term follow‐up. Objectives: To evaluate the safety and reinjury rate of racehorses after intralesional MSC injection in a large study of naturally occurring superficial digital flexor tendinopathy and to compare these data with those published for other treatments. Methods: Safety was assessed clinically, ultrasonographically, scintigraphically and histologically in a cohort of treated cases: 141 client‐owned treated racehorses followed‐up for a minimum of 2 years after return to full work. Reinjury percentages were compared to 2 published studies of other treatments with similar selection criteria and follow‐up. The number of race starts, discipline, age, number of MSCs injected and interval between injury and treatment were analysed. Results: There were no adverse effects of the treatment with no aberrant tissue on histological examination. The reinjury percentage of all racehorses with follow‐up (n = 113) undergoing MSC treatment was 27.4%, with the rate for flat (n = 8) and National Hunt (n = 105) racehorses being 50 and 25.7%, respectively. This was significantly less than published for National Hunt racehorses treated in other ways. No relationship between outcome and age, discipline, number of MSCs injected or injury to implantation interval was found. Conclusions: Whilst recognising the limitations of historical controls, this study has shown that MPC implantation is safe and appears to reduce the reinjury rate after superficial digital flexor tendinopathy, especially in National Hunt racehorses. Potential relevance: This study has provided evidence for the long‐term efficacy of MSC treatment for tendinopathy in racehorses and provides support for translation to human tendon injuries.     

Equine embryonic stem‐like cells and mesenchymal stromal cells have different survival rates and migration patterns following their injection into damaged superficial digital flexor tendon

Reasons for performing study: Injury to the superficial digital flexor tendon (SDFT) is common in racing and sport horses and poor tendon regeneration leads to high reinjury rates. Autologous mesenchymal stromal cells (MSCs) are being used clinically to improve tendon regeneration but they have some practical limitations. Embryonic stem cells (ESCs) may overcome these limitations but their fate following injection into the damaged SDFT is unknown. Objective: To inject MSCs and ESCs into distinct areas of damage in the SDFT and monitor their survival over a 3 month period. Methods: MSCs and ESCs expressing different reporter genes were injected into separate sites of mechanically induced damage in SDFTs. Cell survival and distribution were examined post mortem after 10, 30, 60 and 90 days and host immune responses determined. Results: Neither MSCs nor ESCs produced signs of cell‐mediated immune response or tumour formation. ESC survival was high and numbers were maintained at a constant level over 90 days. ESCs were present at all sites of damage. In contrast, MSCs showed <5% survival at 10 days and numbers declined over the course of the experiment. MSCs were detected only at the site into which they were injected. Conclusions: ESCs survived in greater numbers than MSCs in the damaged tendon and did not induce an immune response, or form tumours at the injection sites in the 90 day time period studied. ESCs also demonstrated an ability to migrate to other areas of damage within the same tendon, whereas MSCs did not. Potential relevance: ESCs can be used allogeneically, therefore providing a possible ‘off the shelf’ source of cells for therapeutic use which overcomes the practical limitations of autologous MSCs. Furthermore, MSCs and ESCs have different survival rates and migration patterns in the damaged tendon, suggesting that they may produce different functional effects. This may have clinical relevance to treating tendon injuries in the horse.     

The propagation of induced tendon lesions in the equine superficial digital flexor tendon: An ex vivo study

Reasons for performing study: Clinical tendon lesions usually enlarge during the first days to weeks after sustaining the injury due to enzymatic and biomechanical influences. Limiting this enlargement would positively influence prognosis related to lesion size. Objectives: To investigate the effect of cyclic loading on the propagation of enzymatically and physically induced tendon lesions and to assess the effect of immobilisation thereon in an ex vivo model. Methods: Equine cadaver limbs with either physically or collagenase‐induced SDFT lesions were placed in a pneumatic loading device. Groups consisted of unloaded limbs, cyclically loaded limbs and cyclically loaded limbs with fibreglass cast immobilisation. Lesion size was evaluated ultrasonographically and macroscopically and load at failure was determined for groups where lesions enlarged. Results: Physically induced lesions did not propagate after cyclical loading and were not further investigated. Collagenase‐induced lesions propagated significantly more after cyclical loading compared to unloaded limbs. This propagation could effectively be reduced by immobilisation through a lower limb cast. Immobilisation did not influence load at failure. Conclusions: The combination of enzymatic and mechanical stimulation caused the lesions to propagate most. Casting appeared effectively to reduce the enlargement of the original tendon lesions in this ex vivo model, while it did not affect ultimate tendon strength. Potential relevance: As prognosis of tendon injuries is related to lesion size, the outcome of this study warrants further investigations in vivo.     

The influence of exercise during growth on ultrasonographic parameters of the superficial digital flexor tendon of young Thoroughbred horses

REASON FOR PERFORMING STUDY: Conditioning by early training may influence the composition of certain musculoskeletal tissues, but very few data exist on its effect during growth on tendon structure and function. OBJECTIVES: To investigate whether conditioning exercise in young foals would lead to any ultrasonographically detectable damage to the superficial digital flexor tendon or an increase in cross-sectional area (CSA). METHODS: Thirty-three Thoroughbred foals reared at pasture were allocated to 2 groups: control (PASTEX) allowed exercise freely at pasture; and CONDEX, also at pasture, began conditioning exercise from mean age 21 days over 1030 m on a purpose-built oval grass track, for 5 days/week until mean age 18 months. Foals were observed daily, and underwent orthopaedic examination monthly. Ultrasonographic images of the superficial digital flexor tendon (SDFT) at the mid-metacarpal level of both forelimbs were obtained in all foals at ages 5, 8, 12, 15 and 18 months. CSA was validated (r(2) = 0.89) by determining CSA from digital photographs of the transected SDFT surface from 12 of the horses necropsied at age 17.1 months. RESULTS: here was no clinical or ultrasonographic evidence of tendonopathy in either group and the greatest increase in mean CSA in both groups occurred between age 5 and 8 months. Across all age categories, there was no significant difference in mean CSA between the left and right limbs, or colts and fillies; there was a trend towards a larger CSA in the CONDEX group (P = 0.058). CONCLUSIONS: There was no conclusive evidence for a structural adaptive hypertrophy of the SDFT, probably because the regimen was insufficiently rigorous or because spontaneous pasture exercise may induce maximal development of energy storing tendons. POTENTIAL RELEVANCE: A moderate amount of early conditioning exercise against a background of constant exercise at pasture is not harmful to the development of the flexor tendons.     

Influence of track surface on the equine superficial digital flexor tendon loading in two horses at high speed trot

Reasons for performing study: Although track surfaces are a risk factor of tendon injuries, their effects on tendon loading at high speed are unknown. Using a noninvasive ultrasonic technique, it is now possible to evaluate the forces in the superficial digital flexor tendon (SDFT) in exercise conditions. Objectives: To compare the effects of an all‐weather waxed track (W) vs. a crushed sand track (S), on the SDFT loading in the trotter horse at high speed. Methods: Two trotter horses were equipped with the ultrasonic device (1 MHz ultrasonic probe, fixed on the palmar metacarpal area of the right forelimb). For each trial, data acquisition was made at 400 Hz and 10 consecutive strides were analysed. In each session, the 2 track surfaces were tested in a straight line. The speed was imposed at 10 m/s and recorded. The right forelimb was also equipped with a dynamometric horseshoe and skin markers. The horse was filmed with a high‐speed camera (600 Hz); all recordings were synchronised. Statistical differences were tested using the GLM procedure (SAS; P<0.05). Results: Maximal tendon force was significantly lower on W compared with S. In addition to maximal force peaks around mid‐stance, earlier peaks were observed, more pronounced on S than on W, at about 13%(horse 2) and 30% (both horses) of the stance phase. Comparison with kinematic data revealed that these early peaks were accompanied by plateaux in the fetlock angle‐time chart. For high tendon forces, the tendon maximal loading rate was significantly lower on W than on S. Conclusions and potential clinical relevance: The all‐weather waxed track appears to induce a lesser and more gradual SDFT loading than crushed sand. The SDFT loading pattern at high speed trot suggests proximal interphalangeal joint movements during limb loading.     

Relationship between the ultrasonographic findings of suspected superficial digital flexor tendon injury and the prevalence of subsequent severe superficial digital flexor tendon injuries in Thoroughbred horses: a retrospective study

The onset of severe injury to the superficial digital flexor tendon (SDFT) is extremely difficult to predict from slight changes in ultrasonographic findings in cases with no apparent clinical signs. This study investigated the relationship between an increased cross-sectional area (CSA) or edema in the subcutaneous tissue around the tendon and the subsequent onset of severe SDFT injury in Thoroughbred racehorses. Horses were classified into three groups based on ultrasound diagnosis (USD) findings: Group A included cases with enlarged tendons; Group B included cases with tendons of normal size but with prominent edema in the peritendinous tissue; and Group C (control group) included cases with no abnormal USD findings. The incidence of subsequent severe tendon injury was significantly higher in the horses in Groups A (25.7%, 28/101) and B (28.3%, 65/212) than in those in Group C (4.9%, 2/41). There were no significant differences in the median period and the median number of races from the first examination to the subsequent tendon injury between Groups A (140 days, 1 race) and B (120 days, 1 race). The results of this study revealed that horses with increased CSA and peritendinous edema are likely to suffer a subsequent severe tendon injury. Also, these two USD findings, i.e., increased CSA and peritendinous edema, indicate the risk of onset of severe SDFT injury.     

Tendonitis of the branches of insertion of the superficial digital flexor tendon in horses

Objective To describe clinical findings, ultrasonographic features and outcome of injury to the branches of insertion of the superficial digital flexor (SDF) tendon in horses.
Design Retrospective study of 14 cases.
Procedure Fourteen Thoroughbred horses with tendonitis affecting the branches of insertion of the SDF tendon were examined for lameness, location and amount of swelling, and the presence of other musculoskeletal abnormalities. The flexor tendons were assessed by ultrasonographic examination, and recommendations were made for management of the cases. Outcome was assessed by re-examination of some horses, direct communication with the owner or trainer, and examination of race records.
Results The lateral SDF branch was affected in 10 horses; the medial branch in three, and both branches in one horse. Two horses had concurrent injuries to the SDF tendon in the metacarpal region of the contralateral limb. Ultrasonographic findings included swelling of the affected SDF branch, peritendinous fluid accumulation, disruption of normal fibre alignment on sagittal scan, and variable loss of echogenicity. As healing occurred, there was return of normal echogenicity, but normal fibre alignment did not return completely and apparent adhesions formed between the affected SDF branch and adjacent structures. Seven of 10 horses which returned to their previous use were able to compete without further tendon injury. Recurrence of injury occurred in one case, and another two horses developed tendonitis in the metacarpal region. One horse was retired from racing but was able to compete at dressage without recurrence of injury. Two horses were retired for breeding without returning to training, and one horse was sold and lost to follow up but did not race.
Conclusion The prognosis is fair for return to previous use following injury to the branches of insertion of the SDF tendon in athletic horses.     

Injection of the insertion of the deep digital flexor tendon in horses using radiographic guidance

Insertional tendinopathies of the DDFT have been reported both as the sole lesion and as part of a multifocal lesion (Dyson et al. 2003). Computed tomography (CT) and magnetic resonance imaging allow specific diagnosis of deep digital flexor tendon lesions within the hoof capsule; however, direct intralesional treatment of such lesions is difficult because of the hoof's rigid structure. A technique designed to mimic intralesional injection of insertional tendinopathies of the DDFT in the standing horse using radiographic guidance was assessed. Radiographic and contrast CT imaging and sectioning of the limbs confirmed accurate injection in all cases although inadvertant administration of injectate into adjacent structures was also evident.     

Tendonitis of branches of the superficial digital flexor tendon in Standardbred racehorses: 15 cases

This case report describes the clinical and ultrasonographic findings and performance outcome of distal tendonitis of the superficial digital flexor tendon (SDFT) in Standardbred racehorses. Cases with distal tendonitis of the SDFT in isolation (not associated with a metacarpal lesion) were reviewed retrospectively. The clinical and ultrasonographic findings and performance outcome were reviewed. The injury was located on the left forelimb in 67% (10/15) of horses and on the right forelimb in 33% (5/15). None of the horses were affected bilaterally. The lateral branch was involved in 80% of the cases (12/15) and medial branch in 20% (3/15). None of the horses were affected biaxially. Mean time between injury and first start ± s.d. was 302 ± 142 days. Returning to racing was observed in 93% of the horses (14/15), with a reinjury rate of 22% (2/9). For horses which raced after the injury, the number of starts, shows and wins was not significantly different before and after injury, regardless of the location of the lesion. Tendonitis of branches of the SDFT in isolation carries a good prognosis in Standardbred racehorses. A higher return to racing and a lower reinjury rate may be expected compared to lesions in the metacarpal region.     

Injuries of the calcaneal insertions of the superficial digital flexor tendon in 19 horses

Reasons for performing study: Injuries of the calcaneal insertions of the superficial digital flexor tendon and their relationship to displacement of the tendon from the calcaneus have not previously been reported. Objectives: To describe findings made on clinical cases with disruption of the calcaneal insertions of the superficial digital flexor tendon (SDFT) including observations on their role in horses with unstable subluxation of the tendon. To describe novel surgical techniques and the results of treatment. Hypotheses: Disruption of the calcaneal insertions of the SDFT is associated with lameness and distension of the calcaneal bursa. Unstable displacement of the SDFT from the calcaneus is a more complex injury than incomplete disruption of one of its calcaneal insertions. Methods: The case records and diagnostic images of horses with lesions involving the calcaneal insertions of the SDFT, which were confirmed by endoscopic evaluation of calcaneal bursa between 2005 and 2009, were reviewed. Results: Nineteen horses were identified including 7 that had unstable displacement of the tendon from the calcaneus. Following endoscopic surgery, 9 of 12 horses with stable tendons and 6 of 7 horses with unstable displaced SDFTs returned to work. Conclusion: Tearing of the calcaneal insertions of the SDFT is associated with lameness and distension of the calcaneal bursa; endoscopic removal of the torn tissue carries a good prognosis. Horses with unstable displacement of the tendon have also disruption of the tendon fibrocartilage cap. Removal of this results in stable subluxation and can return horses to athletic activity. Both lesions can be detected by preoperative ultrasonography. Potential relevance: Tearing of the calcaneal insertions of the SDFT should be included in the differential diagnoses of lame horses with distended calcaneal bursae. Tearing of the tendon fibrocartilage cap in horses with unstable displacement of the SDFT is a plausible explanation of the clinical features of the injury and explains previously unreliable results of reconstructive surgeries. Subtotal resection is a technically demanding technique but appears to offer an improved prognosis.     

Estimation of heritability for superficial digital flexor tendon injury by Gibbs sampling in the Thoroughbred racehorse

The superficial digital flexor tendon (SDFT) injury causes considerable wastage of racing Thoroughbreds. In this study, the heritability of SDFT injury of the forelimbs was estimated in the Thoroughbred racehorses based on the Bayesian analysis with Gibbs sampling using threshold animal models. New horse patients of SDFT injury at the age of 2–5 years accommodated in the training centers in 2005 were used for the analyses. Based on clinical data of 8198 horses, heritability of SDFT was estimated to be the order of 0.17 (posterior mode) to 0.19 ± 0.05 (posterior mean ± posterior SD).     

Tenectomy of the superficial digital flexor tendon as a treatment of suspected septic tendinitis and tenosynovitis of the digital flexor tendon sheath followed by rehabilitation with an orthotic device

A 15-year-old Sports horse gelding was referred for nonweightbearing lameness of the left hindlimb. Septic cellulitis was diagnosed and managed medically. After 14 days, septic tenosynovitis of the digital flexor tendon sheath (DFTS), with septic tendinitis of the superficial (SDFT) and deep (DDFT) digital flexor tendons, became evident. Surgical resection of the intrathecal portion of the septic SDFT was performed. Post-operatively, a half-limb cast was placed on the operated limb for 10 weeks followed by an articulated orthotic support boot during a rehabilitation period of 6 weeks. The horse recovered and regained long-term pasture soundness. Ultrasonography demonstrated the presence of bridging connective tissue in the location of the resected SDFT.     

Deep digital flexor tendon rupture in two horses: A potential complication of comminuted second phalangeal fractures

This case report describes the history, clinical findings, treatment and outcome of 2 horses with damage and eventual rupture of the deep digital flexor tendon as a result of a comminuted second phalangeal fracture. The rupture of the deep digital flexor tendon complicated the treatment and in one horse contributed to its eventual euthanasia. The athletic outcome was limited in the second case and the lack of palmar soft tissue support likely had a significant effect on the stability and biomechanics of the repair.     

Age-related differences in collagen crimp patterns in the superficial digital flexor tendon core region of untrained horses

Objective To measure collagen fibril crimp angles and lengths as well as collagen fibril mass-average diameters in central and peripheral regions of the superficial digital flexor tendon of wild horses, to ascertain any age-related changes in either region in the absence of imposed galloping exercise.
Design Measurements from a random cull of wild horses.
Sample population Superficial digital flexor tendon samples were taken from 23 wild horses ranging in age from two to ten years.
Procedure Horses were divided into 'young' (< 5 years, n = 10), 'middle-aged' (5 to < 10 years, n = 9) and 'old' groups (10+ years, n = 4) and the mean crimp angle, mean crimp length and collagen fibril mass-average diameter calculated for the central region, and for the peripheral region of each group. Differences between groups and regions were analysed using two-tailed t tests.
Results The crimp angle for the central region was found to decrease with age, so that in old horses it was smaller than that for the tendon periphery (P < 0.05). The crimp angle for the latter region did not alter significantly with age. Crimp period lengths and collagen fibril mass-average diameters did not show significant changes with age in either region.
Conclusion Reduction of the crimp angle in the core of the superficial digital flexor tendon occurs normally with age, as tendons of older animals would have undergone a higher number of loading cycles. It is possible that athletic training increases the frequency and/or the magnitude of high loading cycles experienced by the tendon, and may accelerate and worsen the normal load-related ageing process in the superficial digital flexor tendons of young performance horses, particularly in the central regions where lesions usually occur.     

Outcome of conservative and surgical treatment for luxations of the equine superficial digital flexor tendon from the calcaneal tuber

The objective of this study was to report the outcome of horses treated either conservatively or surgically for luxation of the superficial digital flexor tendon (SDFT) from the calcaneal tuber. Medical records of horses with diagnosed SDFT luxations from the calcaneal tuber were reviewed (1993–2015) and long-term follow-up examinations and owner questionnaires performed. Survival to hospital discharge, complications, final SDFT position, soundness and return to intended use were compared between conservatively or surgically treated horses. Following conservative treatment all horses (n = 8) survived to hospital discharge. At long-term follow-up 71.4% (5/7) had returned to intended use. The SDFT was unstable in all of them resulting in a mild mechanical lameness. Nine horses underwent surgical treatment. The SDFT was reduced and maintained in position with a synthetic mesh and sutures (n = 2), with a synthetic mesh, sutures and suture screws (n = 6) or with sutures and suture screws (n = 1). Only 66.7% (6/9) of the horses survived to hospital discharge. Fatal complications including support limb laminitis (1/9), implant infection (1/9), and support limb laminitis plus infection (1/9) occurred. All horses available for long-term follow-up (n = 5) were clinically sound and 80% (4/5) had returned to intended use. Following conservative treatment, a mild mechanical lameness will persist but will not prevent the horses from returning to their intended use. Surgical repair can result in a stable fixation of the SDFT with long-term soundness and return to intended use; however, fatal complications (support limb laminitis, infection) can occur leading to the euthanasia of the horse in the immediate post-operative period.