Johnson SA, Sikes KJ, Johnson JW, Van Zeeland E, Wist S, Santangelo KS, King MR, Frisbie DD.Low load exercise training with blood flow restriction (BFR) has become increasingly used by human physical therapists to prescribe controlled exercise following orthopaedic injury; its effects on the equine superficial digital flexor tendon (SDFT), however, are unknown. Objective: To investigate outcomes of pressure specific BFR walking exercise on uninjured equine SDFT biomechanics and histomorphology. Methods: Controlled in vivo experiment. Methods: Four forelimbs of four horses were exposed to 40 BFR-walk sessions (10-min interval walking) on a treadmill over a 56-day study period with the...
Pu00e9rez Fraile A, Gonzu00e1lez-Cubero E, Martu00ednez-Flu00f3rez S, Olivera ER, Villar-Suu00e1rez V.Musculoskeletal injuries in horses have a great economic impact, predominantly affecting tendons, ligaments, and cartilage, which have limited natural regeneration. Cell therapy, which uses mesenchymal stem cells due to their tissue differentiation properties and anti-inflammatory and immunoregulatory effects, aims to restore damaged tissue. In this manuscript, we performed a systematic review using the Parsifal tool, searching the PubMed and Web of Science databases for articles on regenerative medicine for equine musculoskeletal injuries. Our review covers 17 experimental clinical studies ca...
Anoushepour A, Eftekhari S, Masoudifard M.Superficial digital flexor tendon (SDFT) plays an important role in the locomotion of the horses with flexion of the limbs. In the hind limb, it passes over the calcaneal bone and attaches to medial and lateral surfaces of calcaneous by two bands of connective tissue; while, the medial band is weaker than the lateral one. Occasionally, severe trauma, over-extension or fracture of the calcaneous may cause rupture of the supportive bands leading to tendon luxation. An 11-year-old Thoroughbred jumping gelding with symptoms of lameness in both legs, after examination by an internal specialist vete...
Pechanec MY, Mienaltowski MJ.Equine tendinopathies are challenging because of the poor healing capacity of tendons commonly resulting in high re-injury rates. Within the tendon, different regions - tendon proper (TP) and peritenon (PERI) - contribute to the tendon matrix in differing capacities during injury and aging. Aged tendons have decreased repair potential; the underlying transcriptional and epigenetic changes that occur in the TP and PERI regions are not well understood. The objective of this study was to assess TP and PERI regional differences in adolescent, midlife, and geriatric horses using RNA sequencing and ...
Koch DW, Schnabel LV.Tendon injuries are common in both veterinary and human clinical patients and result in morbidity, pain, and lost athletic performance. Consequently, utilizing naturally occurring injuries in veterinary patients as a comparative model could inform the development of novel therapies and increase translation for the treatment of human tendon injuries. Mesenchymal stem cells (MSCs) have shown considerable efficacy for the treatment of experimental and clinical superficial digital flexor tendon injury in the horse; however, the reinjury rate following treatment can remain high and MSC efficacy in ...
Palomino Lago E, Jelbert ER, Baird A, Lam PY, Guest DJ.Persistent inflammation is associated with the poor regeneration of musculoskeletal tissues. Embryonic stem cells (ESCs) have an attenuated response to inflammatory cytokines, but there are mixed reports on the response of induced pluripotent stem cells (iPSCs) to inflammation. Horses provide a relevant large animal model for studying musculoskeletal tissue diseases and the testing of novel therapies. The aim of this study was to determine if equine iPSCs are responsive to the inflammatory cytokines IL-1β, TNFα and IFN-γ in their undifferentiated state, or following differentiation into ten...
Luo J, Wang Z, Tang C, Yin Z, Huang J, Ruan D, Fei Y, Wang C, Mo X, Li J, Zhang J, Fang C, Li J, Chen X, Shen W.Tendinopathy is a common motor system disease that leads to pain and reduced function. Despite its prevalence, our mechanistic understanding is incomplete, leading to limited efficacy of treatment options. Animal models contribute significantly to our understanding of tendinopathy and some therapeutic options. However, the inadequacies of animal models are also evident, largely due to differences in anatomical structure and the complexity of human tendinopathy. Different animal models reproduce different aspects of human tendinopathy and are therefore suitable for different scenarios. This rev...
Frontiers in geneticsAugust 14, 2023
Volume 14 1201628 doi: 10.3389/fgene.2023.1201628
Momen M, Brauer K, Patterson MM, Sample SJ, Binversie EE, Davis BW, Cothran EG, Rosa GJM, Brounts SH, Muir P. Spontaneous rupture of tendons and ligaments is common in several species including humans. In horses, degenerative suspensory ligament desmitis (DSLD) is an important acquired idiopathic disease of a major energy-storing tendon-like structure. DSLD risk is increased in several breeds, including the Peruvian Horse. Affected horses have often been used for breeding before the disease is apparent. Breed predisposition suggests a substantial genetic contribution, but heritability and genetic architecture of DSLD have not been determined. To identify genomic regions associated with DSLD, we recr...
Shojaee A.Tendons are dense connective tissues that play an important role in the biomechanical function of the musculoskeletal system. The mechanical forces have been implicated in every aspect of tendon biology. Tendon injuries are frequently occurring and their response to treatments is often unsatisfactory. A better understanding of tendon biomechanics and mechanobiology can help develop treatment options to improve clinical outcomes. Recently, tendon tissue engineering has gained more attention as an alternative treatment due to its potential to overcome the limitations of current treatments. This ...
Terzi A, Gallo N, Sibillano T, Altamura D, Masi A, Lassandro R, Sannino A, Salvatore L, Bunk O, Giannini C, De Caro L.Type I collagen physiological scaffold for tissue regeneration is considered one of the widely used biomaterials for tissue engineering and medical applications. It is hierarchically organized: five laterally staggered molecules are packed within fibrils, arranged into fascicles and bundles. The structural organization is correlated to the direction and intensity of the forces which can be loaded onto the tissue. For a tissue-specific regeneration, the required macro- and microstructure of a suitable biomaterial has been largely investigated. Conversely, the function of multiscale structural i...
Beaumont RE, Smith EJ, Zhou L, Marr N, Thorpe CT, Guest DJ.We investigated how Interleukin 1 beta (IL-1β) impacts equine tenocyte function and global gene expression in vitro and determined if these effects could be rescued by pharmacologically inhibiting nuclear factor-κB (NF-B) or interleukin 1 signalling. Equine superficial digital flexor tenocytes were cultured in three-dimensional (3D) collagen gels and stimulated with IL-1β for two-weeks, with gel contraction and interleukin 6 (IL6) measured throughout and transcriptomic analysis performed at day 14. The impact of three NF-B inhibitors on gel contraction and IL6 secretion were measured in 3D ...
Zamboulis DE, Marr N, Lenzi L, Birch HL, Screen HRC, Clegg PD, Thorpe CT.Energy storing tendons such as the human Achilles and equine superficial digital flexor tendon (SDFT) are prone to injury, with incidence increasing with aging, peaking in the 5 decade of life in the human Achilles tendon. The interfascicular matrix (IFM), which binds tendon fascicles, plays a key role in energy storing tendon mechanics, and aging alterations to the IFM negatively impact tendon function. While the mechanical role of the IFM in tendon function is well-established, the biological role of IFM-resident cell populations remains to be elucidated. Therefore, the aim of this study was...
Schade J, de Souza AF, Vincensi LC, Mu00fcller TR, Fonteque JH.The objective of this study was to evaluate and compare the sonographic characteristics of the digital flexor tendons and ligaments of the palmar/plantar of the metacarpal and metatarsal regions in gaited horses, as well as to establish normal reference ultrasound values for Mangalarga Marchador (MM) and Campeiro breeds. Transverse sonographic images were obtained of 50 adult and healthy horses from the MM ( = 25) and Campeiro ( = 25) breeds. The images were taken in six metacarpal/metatarsal zones, and the following measurements were taken: transverse area, circumference, dorsopalmar/plantar ...
Leal Reis I, Lopes B, Sousa P, Sousa AC, Branquinho M, Caseiro AR, Pedrosa SS, Ru00eama A, Oliveira C, Porto B, Atayde L, Amorim I, Alvites R....Tendon and ligament injuries are frequent in sport horses and humans, and such injuries represent a significant therapeutic challenge. Tissue regeneration and function recovery are the paramount goals of tendon and ligament lesion management. Nowadays, several regenerative treatments are being developed, based on the use of stem cell and stem cell-based therapies. In the present study, the preparation of equine synovial membrane mesenchymal stem cells (eSM-MSCs) is described for clinical use, collection, transport, isolation, differentiation, characterization, and application. These cells are ...
Belacic ZA, Sullivan SN, Rice HC, Durgam SS.To investigate the effects of interleukin-1β (IL-1β) and methylprednisolone acetate (MPA) on equine intrabursal deep digital flexor tendon (DDFT) and navicular bone fibrocartilage (NBF) cells in vitro. Methods: Third passage DDFT and NBF cells from 5 healthy donor horses ages 11-17 years euthanized for reasons unrelated to musculoskeletal conditions. Methods: Aggregate cultures were incubated with culture medium alone (control), 10 ng/mL IL-1β, 10 ng/mL IL-1β + 0.05 mg/mL MPA, or 10 ng/mL IL-1β + 0.5 mg/mL MPA for 24 hours. Extracellular matrix (ECM) gene expressions were assessed via rea...
Pechanec MY, Beall JM, Katzman S, Maga EA, Mienaltowski MJ.Tendinopathies remain the leading contributor to career-ending injuries in horses because of the complexity of tendon repair. As such, cell-based therapies like injections of adipose-derived mesenchymal stem cells (ADMSCs, or MSCs) into injured tendons are becoming increasingly popular though their long-term efficacy on a molecular and wholistic level remains contentious. Thus, we co-cultured equine MSCs with intrinsic (tendon proper) and extrinsic (peritenon) tendon cell populations to examine interactions between these cells. Gene expression for common tenogenic, perivascular, and differenti...
Doll CU, Bohner M, Berner D, Buettner K, Horstmeier C, Winter K, Burk J.Low-field magnetic resonance imaging (MRI) has gained increasing importance to monitor equine tendon lesions. Comparing results between studies and cases is hampered, because image analysis approaches vary strongly. This study aimed to improve reliability, comparability and time efficiency of quantitative MRI image analysis. Unassigned: Induced tendon lesions were studied over a 24-week period with 10 follow-up MRI examinations. Signal intensities (SIs) of tendons, tendon lesions, cortical bone and background, as well as lesion cross-sectional areas (CSAs) were measured. Lesion SI standardisat...
Chans-Veres J, Albiu00f1ana-Cunningham J, Quintela JM, Pereira E, Tejero S.Surgery for severe equine cavo-varus is complex and must be individualized. The interindividual phenotypic variability demands a personalized planning of each foot to be operated. The study's primary goal was to evaluate the function and satisfaction of a series of patients with severe equinus cavo-varus deformity who underwent a triplanar tarsectomy and transposition of the posterior tibial tendon in a single stage surgery after a patient specific 3D biomodel planning. A series of 12 feet (5 patients bilaterally) operated with this technique was analyzed. The cohort comprised 2 females (28.5 ...
Marr N, Zamboulis DE, Werling D, Felder AA, Dudhia J, Pitsillides AA, Thorpe CT. The interfascicular matrix (IFM; also known as the endotenon) is critical to the mechanical adaptations and response to load in energy-storing tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT). We hypothesized that the IFM is a tendon progenitor cell niche housing an exclusive cell subpopulation. Immunolabelling of equine superficial digital flexor tendon was used to identify the interfascicular matrix niche, localising expression patterns of CD31 (endothelial cells), Desmin (smooth muscle cells and pericytes), CD146 (interfascicular matrix cells) and LA...
Manfredi JM, Jacob S, Norton E.Endocrine disorders are associated with joint pain and tendon injury in humans, but the effects in the horse are only starting to be understood. Similar patterns of clinical signs and injury appear to affect horses and humans for both orthopedic and endocrine disorders, supporting the use of a one-health approach to tackle these issues. In this Currents in One Health, we will discuss common equine endocrinopathies, current testing recommendations, dietary management, genetic predispositions, and endocrine disorders' effects on performance. Our aim is to use a one-health lens to describe curren...
Smith EJ, Beaumont RE, McClellan A, Sze C, Palomino Lago E, Hazelgrove L, Dudhia J, Smith RKW, Guest DJ.Tendon injuries occur commonly in both human and equine athletes, and poor tendon regeneration leads to functionally deficient scar tissue and an increased frequency of re-injury. Despite evidence suggesting inadequate resolution of inflammation leads to fibrotic healing, our understanding of the inflammatory pathways implicated in tendinopathy remains poorly understood, meaning successful targeted treatments are lacking. Here, we demonstrate IL-1β, TNFα and IFN-γ work synergistically to induce greater detrimental consequences for equine tenocytes than when used individually. This includes ...
James S, Daffy J, Cook J, Samiric T.Fluoroquinolone antibiotics are associated with increased risk of tendinopathy and tendon rupture, which can occur well after cessation of treatment. We have previously reported that the fluoroquinolone ciprofloxacin (CPX) reduced proteoglycan synthesis in equine tendon explants. This study aimed to determine the effects of CPX on proteoglycan catabolism and whether any observed effects are reversible. Equine superficial digital flexor tendon explant cultures were treated for 4 days with 1, 10, 100 or 300 µg/mL CPX followed by 8 days without CPX. The loss of [S]-labelled proteoglycans and che...
Bostru00f6m A, Asplund K, Bergh A, Hyytiu00e4inen H.To explore the scientific evidence for therapeutic ultrasound (TU), we conducted a systematic review of the literature on TU in dogs, horses, donkeys, and cats. Methods: In three major databases, relevant articles published in 1980-2020 were identified. The risk of bias in each article was evaluated. Results: Twenty-four relevant articles on the effects of TU in dogs, nine in horses, two in donkeys, and one in cats were identified. TU usually involved 2-6 treatments weekly for up to 4 weeks. Articles on tendon, ligament, and bone healing, acute aseptic arthritis, osteoarthritis, paraparesis, h...
Depuydt E, Chiers K, Van Hecke L, Saunders J, Martens A, Pille F, Spaas JH.Injuries to equine tendons and ligaments are career-compromising, causing reduced performance and premature retirement. Promising treatment alternatives have been investigated in the field of mesenchymal stem cells (MSCs). In this study, the tissue adherence and protein expression of tenogenic primed mesenchymal stem cells (tpMSCs) after administration to ex vivo tendon and ligament explants is investigated. First, collagen type I (COL I) and smooth muscle actin (SMA) expression was assessed in cytospins prepared from native MSCs and tpMSCs. Second, equine superficial digital flexor tendon and...
Bostru00f6m A, Bergh A, Hyytiu00e4inen H, Asplund K.Extracorporeal shockwave therapy (ECSWT) is increasingly used to treat different types of musculoskeletal conditions in sport and companion animals. To explore the scientific basis for the treatment, we conducted a systematic review of the literature on ECSWT used in horses, dogs, and cats. Methods: Relevant articles published in 1980-2020 were identified from three major databases. Each article was assessed for risk of bias. Results: The review identified 27 relevant articles on the effects of ECSWT in horses, nine in dogs, but none in cats. Typically, ECSWT involved one to three treatment se...
Duddy HR, Schoonover MJ, Hague BA.Tendon and ligament injuries are significant causes of loss of use and early retirement in performance horses. Amniotic fluid and tissue are excellent sources of growth factors and cytokines important in tendon and ligament healing. Thus, an equine-origin liquid amnion allograft (ELAA) may be beneficial in the treatment of equine tendonitis and desmitis. Objectives of this study were to report the outcome achieved (i.e. ability to return to work) for horses diagnosed with tendonitis or desmitis lesions treated with local injection of ELAA and to compare these outcomes to those reported for oth...
Mokry A, Bernhard C, Faulkner J, Colgate VA, Dumoulin M, Pille F, Vanderperren K, Delling U, Oosterlinck M.Forelimb extensor tendon rupture (ETR) in foals is sparsely documented. Objective: To describe clinical and imaging findings, treatment details, and long-term outcome in foals with ETR. Methods: Multicentre retrospective case-series. Methods: Clinical record review of foals with ETR, presented to Faculty of Veterinary Medicine at Ghent University (Belgium), the Clinic for Horses at the University of Veterinary Medicine Hannover (Germany), and Rossdales Equine Hospital (UK) between 2009-2021. Long-term outcome based on structured telephone interview with the owner at the university hospitals an...
Koch DW, Schnabel LV, Ellis IM, Bates RE, Berglund AK.Mesenchymal stem cells (MSCs) secrete paracrine factors and extracellular matrix proteins that contribute to their ability to support tissue healing and regeneration. Both the transcriptome and the secretome of MSCs can be altered by treating the cells with cytokines, but neither have been thoroughly investigated following treatment with the specific cytokine transforming growth factor (TGF)-β2. RNA-sequencing and western blotting were used to compare gene and protein expression between untreated and TGF-β2-treated equine bone marrow-derived MSCs (BM-MSCs). A co-culture system was utilized t...
Cheng HW, Chik TK, Weir J, Chan BP.Damage to the hyaline cartilage of the joint surface and osteochondral fractures are key factors leading to the development of osteoarthritis in racehorses, representing a significant cause of racehorse retirement. To tissue-engineer an osteochondral unit that is suitable for joint repair, incorporation of a zone of calcified cartilage should be considered so as to mimic itscounterpart. To date, equine mesenchymal stem cells (eMSCs) have been reported to have multilineage differentiation potential. Yet the generation of a zone of calcified cartilage using eMSCs has not been reported. This work...
Bernardino PN, Smith WA, Galuppo LD, Mur PE, Cassano JM.Mesenchymal stromal (stem) cells (MSCs) have been studied to treat many common orthopedic injuries in horses. However, there is limited information available on when and how to use this treatment effectively. The aim of this retrospective study is to report case features, treatment protocols, and clinical outcomes in horses treated with MSCs. Methods: 65 horses presenting with tendinous, ligamentous, and articular injuries, and treated with MSCs prepared by a single laboratory between 2016 and 2019. Outcome information was available for 26 horses. Methods: Signalment, clinical signs, diagnosti...
Godwin EE, Young NJ, Dudhia J, Beamish IC, Smith RK.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. Objective: 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...
McCarrel TM, Minas T, Fortier LA.Numerous methods are available for platelet-rich plasma (PRP) generation, but evidence defining the optimum composition is lacking. We hypothesized that leukocyte-reduced PRP would result in lower inflammatory cytokine expression compared with concentrated-leukocyte PRP and that maintaining the platelet:white blood cell (WBC) ratio would compensate for the effect of increased WBC concentration. Methods: Blood and flexor digitorum superficialis tendons were collected from young adult horses. Three PRP groups were generated with the same platelet concentration but different WBC concentrations: i...
Schnabel LV, Mohammed HO, Miller BJ, McDermott WG, Jacobson MS, Santangelo KS, Fortier LA.Platelet rich plasma (PRP) has recently been investigated for use in tissue regeneration studies that seek to utilize the numerous growth factors released from platelet alpha-granules. This study examined gene expression patterns, DNA, and collagen content of equine flexor digitorum superficialis tendon (SDFT) explants cultured in media consisting of PRP and other blood products. Blood and bone marrow aspirate (BMA) were collected from horses and processed to obtain plasma, PRP, and platelet poor plasma (PPP). IGF-I, TGF-beta1, and PDGF-BB were quantified in all blood products using ELISA. Ten...
Thorpe CT, Udeze CP, Birch HL, Clegg PD, Screen HR.Tendons transfer force from muscle to bone. Specific tendons, including the equine superficial digital flexor tendon (SDFT), also store and return energy. For efficient function, energy-storing tendons need to be more extensible than positional tendons such as the common digital extensor tendon (CDET), and when tested in vitro have a lower modulus and failure stress, but a higher failure strain. It is not known how differences in matrix organization contribute to distinct mechanical properties in functionally different tendons. We investigated the properties of whole tendons, tendon fascicles ...
Schnabel LV, Lynch ME, van der Meulen MC, Yeager AE, Kornatowski MA, Nixon AJ.Tendinitis remains a catastrophic injury among athletes. Mesenchymal stem cells (MSCs) have recently been investigated for use in the treatment of tendinitis. Previous work has demonstrated the value of insulin-like growth factor-I (IGF-I) to stimulate cellular proliferation and tendon fiber deposition in the core lesion of tendinitis. This study examined the effects of MSCs, as well as IGF-I gene-enhanced MSCs (AdIGF-MSCs) on tendon healing in vivo. Collagenase-induced bilateral tendinitis lesions were created in equine flexor digitorum superficialis tendons (SDFT). Tendons were treated with ...
Caliari SR, Harley BA.Current surgical and tissue engineering approaches for treating tendon injuries have shown limited success, suggesting the need for new biomaterial strategies. Here we describe the development of an anisotropic collagen-glycosaminoglycan (CG) scaffold and use of growth factor supplementation strategies to create a 3D platform for tendon tissue engineering. We fabricated cylindrical CG scaffolds with aligned tracks of ellipsoidal pores that mimic the native physiology of tendon by incorporating a directional solidification step into a conventional lyophilization strategy. By modifying the freez...
Nixon AJ, Dahlgren LA, Haupt JL, Yeager AE, Ward DL.To assess the potential of adipose-derived nucleated cell (ADNC) fractions to improve tendon repair in horses with collagenase-induced tendinitis. Methods: 8 horses. Methods: Collagenase was used to induce tendinitis in the superficial digital flexor tendon of 1 forelimb in each horse. Four horses were treated by injection of autogenous ADNC fractions, and 4 control horses were injected with PBS solution. Healing was compared by weekly ultrasonographic evaluation. Horses were euthanatized at 6 weeks. Gross and histologic evaluation of tendon structure, fiber alignment, and collagen typing were...
Biewener AA.The stresses acting in muscle-tendon units and ligaments of the forelimb and hindlimb of horses were determined over a range of speed and gait based on recordings of ground reaction forces and limb kinematics. Maximum stresses of 40-50 MPa were calculated to act in several of the principal forelimb (superficial digital flexor (SDF), deep digital flexor (DDF), ulnaris lateralis (UL) and flexor carpi ulnaris/radialis (FCU/R)) and hindlimb tendons (plantaris, DDF) at the fastest galloping speeds recorded (up to 7.4 m s-1). Smaller stresses were found for the gastrocnemius (GAST) tendon (30 MPa) a...
Thorpe CT, Streeter I, Pinchbeck GL, Goodship AE, Clegg PD, Birch HL.Little is known about the rate at which protein turnover occurs in living tendon and whether the rate differs between tendons with different physiological roles. In this study, we have quantified the racemization of aspartic acid to calculate the age of the collagenous and non-collagenous components of the high strain injury-prone superficial digital flexor tendon (SDFT) and low strain rarely injured common digital extensor tendon (CDET) in a group of horses with a wide age range. In addition, the turnover of collagen was assessed indirectly by measuring the levels of collagen degradation mark...
Violini S, Ramelli P, Pisani LF, Gorni C, Mariani P.Mesenchymal stem cells (MSCs) have been recently investigated for their potential use in regenerative medicine. MSCs, in particular, have great potential, as in various reports they have shown pluripotency for differentiating into many different cell types. However, the ability of MSCs to differentiate into tendon cells in vitro has not been fully investigated. Results: In this study, we show that equine bone marrow mesenchymal stem cells (BM-MSCs), defined by their expression of markers such as Oct4, Sox-2 and Nanog, have the capability to differentiate in tenocytes. These differentiated cell...
Payne RC, Hutchinson JR, Robilliard JJ, Smith NC, Wilson AM.We provide quantitative anatomical data on the muscle-tendon units of the equine pelvic limb. Specifically, we recorded muscle mass, fascicle length, pennation angle, tendon mass and tendon rest length. Physiological cross sectional area was then determined and maximum isometric force estimated. There was proximal-to-distal reduction in muscle volume and fascicle length. Proximal limb tendons were few and, where present, were relatively short. By contrast, distal limb tendons were numerous and long in comparison to mean muscle fascicle length, increasing potential for elastic energy storage. W...
Bosch G, van Schie HT, de Groot MW, Cadby JA, van de Lest CH, Barneveld A, van Weeren PR.Tendon injuries are notorious for their slow and functionally inferior healing. Intratendinous application of platelet-rich plasma (PRP) has been reported to stimulate the repair process of tendon injuries, but there is little conclusive evidence for its effectiveness. A placebo-controlled experimental trial was performed to test the hypothesis that a single intratendinous PRP treatment enhances the quality of tendon repair, as evidenced by improved biochemical, biomechanical, and histological tissue properties. In six horses, tendon lesions were created surgically in the Superficial Digital F...
White LM, Sussman MS, Hurtig M, Probyn L, Tomlinson G, Kandel R.To prospectively assess T2 mapping characteristics of normal articular cartilage and of cartilage at sites of arthroscopic repair, including comparison with histologic results and collagen organization assessed at polarized light microscopy (PLM). Methods: Study protocol was compliant with the Canadian Council on Animal Care Guidelines and approved by the institutional animal care committee. Arthroscopic osteochondral autograft transplantation (OAT) and microfracture arthroplasty (MFx) were performed in knees of 10 equine subjects (seven female, three male; age range, 3-5 years). A site of art...
Williams RB, Harkins LS, Hammond CJ, Wood JL.For improvements to the safety and welfare of racehorses to be possible, it is essential to have access to basic descriptive information about the veterinary incidents encountered during horseracing. A 3 year surveillance study (1996-1998) was conducted by The Jockey Club into racing injuries, other postrace clinical problems and fatalities from all 59 British racecourses (mainland Britain only) to identify risk factors. During the survey there were 222,993 racing starts: 106,897 starts in flat races on turf (47.9%), 26,519 starts in flat races on all-weather surfaces (11.9%), 30,932 starts in...
Thorpe CT, Clegg PD, Birch HL.Tendon injury is one of the most common causes of wastage in the performance horse; the majority of tendon injuries occur to the superficial digital flexor tendon (SDFT) whereas few occur to the common digital extensor tendon. This review outlines the epidemiology and aetiology of equine tendon injury, reviews the different functions of the tendons in the equine forelimb and suggests possible reasons for the high rate of failure of the SDFT. An understanding of the mechanisms leading to matrix degeneration and subsequent tendon gross failure is the key to developing appropriate treatment and p...
Gaspar D, Spanoudes K, Holladay C, Pandit A, Zeugolis D.The last decade has seen significant developments in cell therapies, based on permanently differentiated, reprogrammed or engineered stem cells, for tendon injuries and degenerative conditions. In vitro studies assess the influence of biophysical, biochemical and biological signals on tenogenic phenotype maintenance and/or differentiation towards tenogenic lineage. However, the ideal culture environment has yet to be identified due to the lack of standardised experimental setup and readout system. Bone marrow mesenchymal stem cells and tenocytes/dermal fibroblasts appear to be the cell populat...
Guest DJ, Smith MR, Allen WR.Autologous mesenchymal progenitor cells (MPCs) purified from bone marrow aspirates are being used in the treatment of superficial digital flexor tendon (SDFT) injuries in the horse with promising results. In this study the fate of autologous and allogeneic MPCs following injection into the SDFT was monitored by stable transfection of MPCs with green fluorescent protein (GFP). Small lesions were created manually in one forelimb SDFT of 2 horses and injected with autologous MPCs, allogeneic MPCs or bone marrow supernatant alone. Post mortem examinations performed after 10 or 34 days revealed GFP...
Thorpe CT, Udeze CP, Birch HL, Clegg PD, Screen HR.Age-related tendinopathy is common in both humans and horses; the initiation and progression of which is similar between species. The majority of tendon injuries occur to high-strain energy storing tendons, such as the human Achilles tendon and equine superficial digital flexor (SDFT). By contrast, the low-strain positional human anterior tibialis tendon and equine common digital extensor (CDET) are rarely injured. It has previously been established that greater extension occurs at the fascicular interface in the SDFT than in the CDET; this may facilitate the large strains experienced during l...
Smith RK.Optimal management of tendon overuse injuries in equine and human athletes should avoid the formation of excessive scar tissue, regenerate normal tendon matrix, and reduce re-injury rates. We hypothesized that the implantation of marrow-derived stromal stem cells (BM-MSCs), in far greater numbers than are present normally within tendon tissue, would synthesize a matrix more closely resembling tendon matrix than scar tissue, and hence increase the capacity to return to performance successfully. This article reviews the technique used clinically in the horse and the current outcome data for hors...
Lomas AJ, Ryan CN, Sorushanova A, Shologu N, Sideri AI, Tsioli V, Fthenakis GC, Tzora A, Skoufos I, Quinlan LR, O'Laighin G, Mullen AM, Kelly JL....Tendon injuries represent a significant clinical burden on healthcare systems worldwide. As the human population ages and the life expectancy increases, tendon injuries will become more prevalent, especially among young individuals with long life ahead of them. Advancements in engineering, chemistry and biology have made available an array of three-dimensional scaffold-based intervention strategies, natural or synthetic in origin. Further, functionalisation strategies, based on biophysical, biochemical and biological cues, offer control over cellular functions; localisation and sustained relea...
Wilson AM, McGuigan MP, Su A, van Den Bogert AJ.The muscular work of galloping in horses is halved by storing and returning elastic strain energy in spring-like muscle-tendon units.These make the legs act like a child's pogo stick that is tuned to stretch and recoil at 2.5 strides per second. This mechanism is optimized by unique musculoskeletal adaptations: the digital flexor muscles have extremely short fibres and significant passive properties, whereas the tendons are very long and span several joints. Length change occurs by a stretching of the spring-like digital flexor tendons rather than through energetically expensive length changes...
Smith RK, Zunino L, Webbon PM, Heinegård D.A protein prominent in guanidine hydrochloride extracts of adult bovine and equine digital flexor tendons was confirmed to be Cartilage Oligomeric Matrix Protein (COMP) by non-reducing and reducing SDS-PAGE, reaction with rabbit anti-COMP polyclonal antiserum on Western blots, trypsin digestion followed by HPLC on a C2/C18 column, and identification of COMP mRNA from tendon on Northern blots. Immunohistochemistry and Western blots of extracts showed COMP to be present in all regions of digital flexor tendons. Equine tendon COMP was purified by ion exchange chromatography and gel filtration and...
Thorpe CT, Peffers MJ, Simpson D, Halliwell E, Screen HR, Clegg PD.Tendon is a simple aligned fibre composite, consisting of collagen-rich fascicles surrounded by a softer interfascicular matrix (IFM). The composition and interactions between these material phases are fundamental in ensuring tissue mechanics meet functional requirements. However the IFM is poorly defined, therefore tendon structure-function relationships are incompletely understood. We hypothesised that the IFM has a more complex proteome, with faster turnover than the fascicular matrix (FM). Using laser-capture microdissection and mass spectrometry, we demonstrate that the IFM contains more ...
Dudhia J, Scott CM, Draper ER, Heinegu00e5rd D, Pitsillides AA, Smith RK.Age-associated and degenerative loss of functional integrity in soft tissues develops from effects of cumulative and subtle changes in their extracellular matrix (ECM). The highly ordered tendon ECM provides the tissue with its tensile strength during loading. As age and exercise collide in the high incidence of tendinopathies, we hypothesized that aged tendons fail due to cumulative damage resulting from a combination of diminished matrix repair and fragmentation of ECM proteins induced by prolonged cyclical loading, and that this is an active cell-mediated process. We developed an equine ten...
Guest DJ, Smith MR, Allen WR.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 reporte...
Sivaguru M, Durgam S, Ambekar R, Luedtke D, Fried G, Stewart A, Toussaint KC.Fourier transform-second harmonic generation (FT-SHG) imaging is used as a technique for evaluating collagenase-induced injury in horse tendons. The differences in collagen fiber organization between normal and injured tendon are quantified. Results indicate that the organization of collagen fibers is regularly oriented in normal tendons and randomly organized in injured tendons. This is further supported through the use of additional metrics, in particular, the number of dark (no/minimal signal) and isotropic (no preferred fiber orientation) regions in the images, and the ratio of forward-to-...
Richardson LE, Dudhia J, Clegg PD, Smith R.Stem cells have evoked considerable excitement in the animal-owning public because of the promise that stem cell technology could deliver tissue regeneration for injuries for which natural repair mechanisms do not deliver functional recovery and for which current therapeutic strategies have minimal effectiveness. This review focuses on the current use of stem cells within veterinary medicine, whose practitioners have used mesenchymal stem cells (MSCs), recovered from either bone marrow or adipose tissue, in clinical cases primarily to treat strain-induced tendon injury in the horse. The backgr...
Thorpe CT, Godinho MSC, Riley GP, Birch HL, Clegg PD, Screen HRC.While the predominant function of all tendons is to transfer force from muscle to bone and position the limbs, some tendons additionally function as energy stores, reducing the cost of locomotion. Energy storing tendons experience extremely high strains and need to be able to recoil efficiently for maximum energy storage and return. In the equine forelimb, the energy storing superficial digital flexor tendon (SDFT) has much higher failure strains than the positional common digital extensor tendon (CDET). However, we have previously shown that this is not due to differences in the properties of...
Patterson-Kane JC, Becker DL, Rich T.The equine superficial digital flexor tendon (SDFT) is a frequently injured structure that is functionally and clinically equivalent to the human Achilles tendon (AT). Both act as critical energy-storage systems during high-speed locomotion and can accumulate exercise- and age-related microdamage that predisposes to rupture during normal activity. Significant advances in understanding of the biology and pathology of exercise-induced tendon injury have occurred through comparative studies of equine digital tendons with varying functions and injury susceptibilities. Due to the limitations of in-...
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