The equine model refers to the use of horses as a biological model in scientific research to study various physiological and pathological processes. Horses are utilized in research due to their unique physiological characteristics, which can parallel certain aspects of human health and disease. This model is applied in studies ranging from musculoskeletal disorders and respiratory diseases to metabolic syndromes and reproductive health. Research involving equine models often investigates disease mechanisms, therapeutic interventions, and preventative strategies. This page gathers peer-reviewed research studies and scholarly articles that explore the application, benefits, and limitations of using horses as models in scientific research, providing insights into equine and comparative biomedical studies.
Verhaar N, de Buhr N, von Köckritz-Blickwede M, Hewicker-Trautwein M, Pfarrer C, Mazzuoli-Weber G, Schulte H, Kästner S.Ischaemic postconditioning (IPoC) refers to brief periods of reocclusion of blood supply following an ischaemic event. This has been shown to ameliorate ischaemia reperfusion injury in different tissues, and it may represent a feasible therapeutic strategy for ischaemia reperfusion injury following strangulating small intestinal lesions in horses. The objective of this study was to assess the degree cell death, inflammation, oxidative stress, and heat shock response in an equine experimental jejunal ischaemia model with and without IPoC. Methods: In this randomized, controlled, experimental in...
Rosengren MK, Sigurðardóttir H, Eriksson S, Naboulsi R, Jouni A, Novoa-Bravo M, Albertsdóttir E, Kristjánsson Þ, Rhodin M, Viklund Å, Velie BD....The back plays a vital role in horse locomotion, where the spine functions as a spring during the stride cycle. A complex interaction between the spine and the muscles of the back contribute to locomotion soundness, gait ability, and performance of riding and racehorses. Conformation is commonly used to select horses for breeding and performance in multiple horse breeds, where the back and croup conformation plays a significant role. The conformation of back and croup plays an important role on riding ability in Icelandic horses. However, the genes behind this trait are still unknown. Therefor...
Yin NH, McCarthy I, Birch HL.Human Achilles tendon is composed of three smaller sub-tendons and exhibits non-uniform internal displacements, which decline with age and after injury, suggesting a potential role in the development of tendinopathies. Studying internal sliding behaviour is therefore important but difficult in human Achilles tendon. Here we propose the equine deep digital flexor tendon (DDFT) and its accessory ligament (AL) as a model to understand the sliding mechanism. The AL-DDFT has a comparable sub-bundle structure, is subjected to high and frequent asymmetric loads and is a natural site of injury similar...
Smith RKW, McIlwraith CW.Tendinopathy remains one of the most common musculoskeletal disorders affecting both human and equine athletes and presents a considerable therapeutic challenge. The following workshop report comes from the third Dorothy Havemeyer Symposium of Tendinopathy which provided a unique overview of our current understanding of both the basic science and the clinical challenges for diagnosing and treating tendinopathy in both species. Pathologically, tendon demonstrates alterations in both cellular, molecular, structural, and biomechanical features, leading to a spectrum of pathological endotypes. To ...
Brooks SA.The sheer diversity of heritable physiological traits, and the ingenuity of genome derived research technologies, extends the study of genetics to impact diverse scientific fields. Equine science is no exception, experiencing a number of genome-enabled discoveries that spur further research in areas like nutrition, reproduction, and exercise physiology. Yet unexpected findings, especially those that over-turn commonly held beliefs in the horse industry, can create challenges in outreach, education and communication with stakeholders. For example, studies of ancient DNA revealed that the oldest...
Cequier A, Sanz C, Rodellar C, Barrachina L.The differentiation ability of mesenchymal stem cells (MSCs) initially raised interest for treating musculoskeletal injuries in horses, but MSC paracrine activity has widened their scope for inflammatory and immune-mediated pathologies in both equine and human medicine. Furthermore, the similar etiopathogenesis of some diseases in both species has advanced the concept of "One Medicine, One Health". This article reviews the current knowledge on the use of MSCs for equine pathologies beyond the locomotor system, highlighting the value of the horse as translational model. Ophthalmologic and repro...
Yuen KY, Bielefeldt-Ohmann H.Ross River virus (RRV) has recently been suggested to be a potential emerging infectious disease worldwide. RRV infection remains the most common human arboviral disease in Australia, with a yearly estimated economic cost of $4.3 billion. Infection in humans and horses can cause chronic, long-term debilitating arthritogenic illnesses. However, current knowledge of immunopathogenesis remains to be elucidated and is mainly inferred from a murine model that only partially resembles clinical signs and pathology in human and horses. The epidemiology of RRV transmission is complex and multifactorial...
Meeremans M, Van Damme L, De Spiegelaere W, Van Vlierberghe S, De Schauwer C.(1) Background: Tendinopathy is a common injury in both human and equine athletes. Representative in vitro models are mandatory to facilitate translation of fundamental research into successful clinical treatments. Natural biomaterials like gelatin provide favorable cell binding characteristics and are easily modifiable. In this study, methacrylated gelatin (gel-MA) and norbornene-functionalized gelatin (gel-NB), crosslinked with 1,4-dithiotreitol (DTT) or thiolated gelatin (gel-SH) were compared. (2) Methods: The physicochemical properties (H-NMR spectroscopy, gel fraction, swelling ratio, an...
De Clercq E, Den Hondt S, De Baere C, Martens AM.To compare the effect of multiple wound dressings on microbial growth in a perfused equine wound model. Methods: Abdominal musculocutaneous flaps from 16 equine cadavers. Methods: 8 full-thickness skin wound covered were created in each flap. Tissues were perfused with saline (0.9% NaCl) solution. Wounds were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (106 CFUs), incubated, and covered with a dressing containing activated charcoal, boric acid, cadexomer iodine, calcium alginate, manuka honey, nanoparticle silver, or polyhexamethylene biguanide ...
Lee AKK, Uhl EW, Osborn ML.Therapies based upon whole-body biomechanical assessments are successful for injury prevention and rehabilitation in human athletes. Similar approaches have rarely been used to study equine athletic injury. Degenerative osteoarthritis caused by mechanical stress can originate from chronic postural dysfunction, which, because the primary dysfunction is often distant from the site of tissue injury, is best identified through modeling whole-body biomechanics. To characterize whole-body equine kinematics, a realistic skeletal model of a horse was created from equine computed tomography (CT) data t...
Fenner MF, Gatta G, Sattler S, Kuiper M, Hesselkilde EM, Adler DMT, Smerup M, Schotten U, Sørensen U, Diness JG, Jespersen T, Verheule S....Small-conductance Ca2+-activated K+ (KCa2) channels have been proposed as a possible atrial-selective target to pharmacologically terminate atrial fibrillation (AF) and to maintain sinus rhythm. However, it has been hypothesized that the importance of the KCa2 current-and thereby the efficacy of small-conductance Ca2+-activated K+ current (I K,Ca) inhibition-might be negatively related to AF duration and the extent of AF-induced remodeling. Unassigned: To address the hypothesis of the efficacy of I K,Ca inhibition being dependent on AF duration, the anti-arrhythmic properties of the I K,Ca inh...
Logan AA, Nielsen BD, Manfredi JM, Robison CI.Short sprints performed during growth can increase bone strength, mineral density, and cortical widths, but their impact on joint health is not fully understood. Some studies have found joints of young animals are damaged by forced sprints, while others found confinement hindered joint development. This study aimed to determine the impact of short sprints on synovial fluid neopeptide collagenase cleavage of type I and II collagen (C1,2C) and cartilage glycosaminoglycan (GAG) content. Calves were used as a model for young horses in this terminal study. Twenty-four Holstein bull calves were assi...
Oláh T, Cai X, Michaelis JC, Madry H.The human knee is a complex joint, and affected by a variety of articular cartilage disorders. Large animal models are critical to model the complex disease mechanisms affecting a functional joint. Species-dependent differences highly affect the results of a pre-clinical study and need to be considered, necessitating specific knowledge not only of macroscopic and microscopic anatomical and pathological aspects, but also characteristics of their individual gait and joint movements. Methods: Literature search in Pubmed. Conclusions: This narrative review summarizes the most relevant anatomical s...
Legere RM, Cohen ND, Poveda C, Bray JM, Barhoumi R, Szule JA, de la Concha-Bermejillo A, Bordin AI, Pollet J.Vaccines and therapeutics using in vitro transcribed mRNA hold enormous potential for human and veterinary medicine. Transfection agents are widely considered to be necessary to protect mRNA and enhance transfection, but they add expense and raise concerns regarding quality control and safety. We found that such complex mRNA delivery systems can be avoided when transfecting epithelial cells by aerosolizing the mRNA into micron-sized droplets. In an equine in vivo model, we demonstrated that the translation of mRNA into a functional protein did not depend on the addition of a polyethylenimine (...
Catalán J, Yánez-Ortiz I, Gacem S, Papas M, Bonet S, Rodríguez-Gil JE, Yeste M, Miró J.Previous research has determined that irradiation of mammalian sperm with red light increases motility, mitochondrial activity, and fertilization capacity. In spite of this, no study has considered the potential influence of the color of the straw and the extender used. Therefore, this study tests the hypothesis that the response of mammalian sperm to red light is influenced by the color of the straw and the turbidity/composition of the extender. Using the horse as a model, 13 ejaculates from 13 stallions were split into two equal fractions, diluted with Kenney or Equiplus extender, and stored...
Kearney CM, Korthagen NM, Plomp SGM, Labberté MC, de Grauw JC, van Weeren PR, Brama PAJ.Intra-articular triamcinolone acetonide is a widely used treatment for joint inflammation despite limited scientific evidence of its efficacy. Objective: To investigate if intra-articular triamcinolone acetonide has sustained anti-inflammatory effects using an equine model of repeated joint inflammation. Methods: Randomised controlled experimental study. Methods: For three consecutive cycles 2 weeks apart, inflammation was induced in both middle carpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After the first LPS injection only, treatment with 12 mg triamcinolone...
Rowland AL, Miller D, Berglund A, Schnabel LV, Levine GJ, Antczak DF, Watts AE.Allogeneic mesenchymal stromal cells (MSCs) have been used clinically for decades, without cross-matching, on the assumption that they are immune-privileged. In the equine model, we demonstrate innate and adaptive immune responses after repeated intra-articular injection with major histocompatibility complex (MHC) mismatched allogeneic MSCs, but not MHC matched allogeneic or autologous MSCs. We document increased peri-articular edema and synovial effusion, increased synovial cytokine and chemokine concentrations, and development of donor-specific antibodies in mismatched recipients compared wi...
Hisey E, Ross PJ, Meyers SA.OCT4 is a core transcription factor involved in pluripotency maintenance in the early mammalian embryo. The POU5F1 gene that encodes the OCT4 protein is highly conserved across species, suggesting conserved function. However, studies in several species including mice, cattle, and pigs, suggest that there are differences in where and when OCT4 is expressed. Specifically, in the horse, several studies have shown that exposure to the uterine environment may be necessary to induce OCT4 expression restriction to the inner cell mass (ICM) of the developing embryo, suggesting that there may be equine...
Sparks HD, Sigaeva T, Tarraf S, Mandla S, Pope H, Hee O, Di Martino ES, Biernaskie J, Radisic M, Scott WM.The equine distal limb wound healing model, characterized by delayed re-epithelialization and a fibroproliferative response to wounding similar to that observed in humans, is a valuable tool for the study of biomaterials poised for translation into both the veterinary and human medical markets. In the current study, we developed a novel method of biaxial biomechanical testing to assess the functional outcomes of healed wounds in a modified equine model and discovered significant functional and structural differences in both unwounded and injured skin at different locations on the distal limb t...
Armando F, Godizzi F, Razzuoli E, Leonardi F, Angelone M, Corradi A, Meloni D, Ferrari L, Passeri B.Squamous cell carcinoma (SCC) is one of the most frequent tumors of skin and muco-cutaneous junctions in the horse. Equine papillomavirus type 2 (EcPV2) has been detected in equine SCC of the oral tract and genitals, and recently also in the larynx. As human squamous cell carcinoma of the larynx (SCCL), it is strongly etiologically associated with high-risk papillomavirus (h-HPV) infection. This study focuses on tumor cells behavior in a naturally occurring tumor that can undergo the so-called epithelial to mesenchymal transition (EMT). A SCCL in a horse was investigated by immunohistochemistr...
Harman RM, Patel RS, Fan JC, Park JE, Rosenberg BR, Van de Walle GR.The efficacy of mesenchymal stromal cell (MSC) therapy is thought to depend on the intrinsic heterogeneity of MSC cultures isolated from different tissue sources as well as individual MSCs isolated from the same tissue source, neither of which is well understood. To study this, we used MSC cultures isolated from horses. The horse is recognized as a physiologically relevant large animal model appropriate for translational MSC studies. Moreover, due to its large size the horse allows for the simultaneous collection of adequate samples from multiple tissues of the same animal, and thus, for the u...
McCoy AM, Kemper AM, Boyce MK, Brown MP, Trumble TN.Post-traumatic osteoarthritis (PTOA) is a common and significant problem in equine athletes. It is a disease of the entire joint, with the synovium thought to be a key player in disease onset and progression due to its role in inflammation. The development of effective tools for early diagnosis and treatment of PTOA remains an elusive goal. Altered gene expression represents the earliest discernable disease-related change, and can provide valuable information about disease pathogenesis and identify potential therapeutic targets. However, there is limited work examining global gene expression c...
Witkowska-Piłaszewicz O, Pingwara R, Winnicka A.Physical activity has an influence on a variety of processes in an athlete's organism including the immune system. Unfortunately, there is a lack of studies regarding racehorse immune cells, especially when the horse model is compared to human exercise physiology. The aim of the study was to determine changes in immune cell proliferation, lymphocyte populations, and monocyte functionality in trained and untrained racehorses after exercise. In this study, field data were collected. The cells from 28 racehorses (14 untrained and 14 well-trained) were collected before and after exercise (800 m at...
Davis KU, Sheats MK.Asthma is a common and debilitating chronic airway disease that affects people and horses of all ages worldwide. While asthma in humans most commonly involves an excessive type 2 immune response and eosinophilic inflammation, neutrophils have also been recognized as key players in the pathophysiology of asthma, including in the severe asthma phenotype where neutrophilic inflammation predominates. Severe equine asthma syndrome (sEAS) features prominent neutrophilic inflammation and has been increasingly used as a naturally occurring animal model for the study of human neutrophilic asthma. This...
Kaynarcalidan O, Oğuzoğlu TÇ.Papillomaviruses are oncogenic DNA viruses and induce hyperplastic benign lesions of both cutaneous and mucosal tissues in their various hosts, including many domestic and wild animals as well as humans. There are some Papillomavirus genotypes that can infect hosts different from their own, such as BPV 1 and BPV 2 originated from cattle, which can also infect horses and are responsible for fibroblastic tumours in horses. This review article summarizes the origin and evolution of papillomaviruses as an etiological agent in the historical process. The main focus in this review is the evaluation ...
Rizzo M, du Preez N, Ducheyne KD, Deelen C, Beitsma MM, Stout TAE, de Ruijter-Villani M.Aneuploidy of meiotic origin is a major contributor to age-related subfertility and an increased risk of miscarriage in women. Although age-related aneuploidy has been studied in rodents, the mare may be a more appropriate animal model to study reproductive aging. Similar to women, aged mares show reduced fertility and an increased incidence of early pregnancy loss; however, it is not known whether aging predisposes to aneuploidy in equine oocytes. We evaluated the effect of advanced mare age on (1) gene expression for cohesin components, (2) incidence of aneuploidy and (3) chromosome centrome...
Ben Hamouda S, Vargas A, Boivin R, Miglino MA, da Palma RK, Lavoie JP.Severe asthma is associated with an increased airway smooth muscle (ASM) mass and altered composition of the extracellular matrix (ECM). Studies have indicated that ECM-ASM cell interactions contribute to this remodeling and its limited reversibility with current therapy. Three-dimensional matrices allow the study of complex cellular responses to different stimuli in an almost natural environment. Our goal was to obtain acellular bronchial matrices and then develop a recellularization protocol with ASM cells. We studied equine bronchi as horses spontaneously develop a human asthma-like disease...
Thompson RE, Johnson AK, Dini P, Turco MY, Prado TM, Premanandan C, Burton GJ, Ball BA, Whitlock BK, Pukazhenthi BS.The endometrium, the inner uterine lining, is composed of cell layers that come in direct contact with an embryo during early pregnancy and later with the fetal placenta. The endometrium is responsible for signals associated with normal reproductive cyclicity as well as maintenance of pregnancy. In the mare, functionally competent in vitro models of the endometrium have not been successful. Furthermore, the ability to study various reproductive processes in vitro may allow critical evaluation of signaling pathways involved in the reproductive diseases of animals that cannot be handled frequent...
Porcellato I, Mecocci S, Mechelli L, Cappelli K, Brachelente C, Pepe M, Orlandi M, Gialletti R, Passeri B, Ferrari A, Modesto P, Ghelardi A....Penile squamous cell carcinomas (SCCs) are common tumors in older horses, with poor prognosis mostly due to local invasion and recurrence. These tumors are thought to be mainly caused by papillomavirus type 2 (EcPV-2). The aim of this study is to characterize the tumor immune environment (TIME) in equine penile tumors. Equine penile epithelial tumors (17 epSCCs; 2 carcinomas , CIS; 1 papilloma, P) were retrospectively selected; immune infiltrate was assessed by histology and immunohistochemistry; RT-qPCR tested the expression of selected chemokines and EcPV-2 DNA and RNA. The results confirme...
Powell DG, Dwyer RM, Traub-Dargatz JL, Fulker RH, Whalen JW, Srinivasappa J, Acree WM, Chu HJ.To determine safety, immunogenicity, and efficacy of an inactivated equine rotavirus vaccine. Methods: Prospective randomized controlled trial. Methods: 316 pregnant Thoroughbred mares during the first year of the study and 311 during the second year. Methods: During the first year, mares received 3 doses of vaccine or placebo, IM, at 8, 9, and 10 months of gestation. Serum neutralizing antibody titers were measured before vaccination and 1 and 35 days after foaling. Antibody titers were measured in foals 1, 7, 35, 60, 90, and 120 days after birth. During the second year, mares that had been v...
Cappelli K, Felicetti M, Capomaccio S, Nocelli C, Silvestrelli M, Verini-Supplizi A.Athletic performance is both a stress factor and an adaptive response to exercise that may be modulated by training, reduce inflammation and help prevent disease. Studies on the endocrinology of exercise and training have demonstrated the existence of an integrated metabolic network of hormone and cytokine regulation. Subsequent molecular studies have shown that repeated bouts of exercise may establish new basal levels of gene expression at rest. The Thoroughbred horse may be a useful 'exercise model' for inter-individual comparisons between subjects with homogeneous genetic and environmental ...
Pfeiffenberger M, Bartsch J, Hoff P, Ponomarev I, Barnewitz D, Thöne-Reineke C, Buttgereit F, Gaber T, Lang A.Fractures in horses-whether simple fractures with just one clean break, or incomplete greenstick with stress fractures, or complications such as shattered bones can all be either minimal or even catastrophic. Thus, improvement in fracture healing is a hallmark in equine orthopedics. The fracture healing process implements a complex sequence of events including the initial inflammatory phase removing damaged tissue, re-establishment of vessels and mesenchymal stromal cells, a soft and hard callus phase closing the fracture gap as well as the remodeling phase shaping the bone to a scar-free tiss...
Hausberger M, Muller C, Lunel C.It has been repeatedly hypothesized that job characteristics are related to changes in personality in humans, but often personality models still omit effects of life experience. Demonstrating reciprocal relationships between personality and work remains a challenge though, as in humans, many other influential factors may interfere. This study investigates this relationship by comparing the emotional reactivity of horses that differed only by their type of work. Horses are remarkable animal models to investigate this question as they share with humans working activities and their potential diff...
Oreff GL, Fenu M, Vogl C, Ribitsch I, Jenner F.For research on tendon injury, many different animal models are utilized; however, the extent to which these species simulate the clinical condition and disease pathophysiology has not yet been critically evaluated. Considering the importance of inflammation in tendon disease, this study compared the cellular and molecular features of inflammation in tenocytes of humans and four common model species (mouse, rat, sheep, and horse). While mouse and rat tenocytes most closely equalled human tenocytes' low proliferation capacity and the negligible effect of inflammation on proliferation, the wound...
Huser CA, Davies ME.The objective of this study was the development and characterization of an in vitro model of the initiation of traumatic osteoarthritis (OA). Articular cartilage was obtained from seven healthy horses and from four horses diagnosed with OA. Cartilage disks were subjected to a single-impact load (500 g from 25, 50, or 100 mm) using a simple drop-tower device and cultured in vitro for up to 20 days. Cartilage sections were examined histologically to observe surface damage and proteoglycan loss. Percentage cell death was determined using TUNEL, release of glycosaminoglycans (GAG) to the medium wa...
Giaretta E, Munerato M, Yeste M, Galeati G, Spinaci M, Tamanini C, Mari G, Bucci D.Setting an open-access computer assisted sperm analysis (CASA) may benefit the evaluation of motility in mammalian sperm, especially when economic constraints do not allow the use of a commercial system. There have been successful attempts to develop such a device in Zebra fish sperm and the system has been used in very few studies on mammalian spermatozoa. Against this background, the present study aimed at developing an open-access CASA system for mammalian sperm using the horse as a model and based upon the Image J software previously established for Zebra fish sperm. Along with determining...
Hillmann A, Ahrberg AB, Brehm W, Heller S, Josten C, Paebst F, Burk J.Multipotent mesenchymal stromal cells (MSCs) have gained tremendous attention as potential therapeutic agents for the treatment of orthopedic diseases. Promising results have been obtained after application of MSCs for treatment of tendon and joint disease in the equine model, making it appear favorable to use these results as a basis for the translational process of the therapy. However, while the horse is considered a highly suitable model for orthopedic diseases, knowledge is lacking regarding the level of analogy of equine MSCs and their human counterparts. Therefore, the aim of this study...
Nixon AJ, Rickey E, Butler TJ, Scimeca MS, Moran N, Matthews GL.Autologous chondrocyte implantation (ACI) has improved outcome in long-term studies of joint repair in man. However, ACI requires sutured periosteal flaps to secure the cells, which precludes minimally-invasive implantation, and introduces complications with arthrofibrosis and graft hypertrophy. This study evaluated ACI on a collagen type I/III scaffold (matrix-induced autologous chondrocyte implantation; MACI(®)) in critical sized defects in the equine model. Methods: Chondrocytes were isolated from horses, expanded and seeded onto a collagen I/III membrane (ACI-Maix™) and implanted into o...
Woode GN, Bew ME, Dennis MJ.Inoculation at birth with a live attenuated strain of a bovine rotavirus isolated in the USA (scourvax-reo) induced protection in five gnotobiotic calves seven to 21 days later against a UK isolate of pathogenic bovine rotavirus. However, no protection was induced in three calves challenged three to five days after vaccination. There was a close antigenic relationship demonstrated between the two bovine rotavirus isolates. In contrast only one of three gnotobiotic calves inoculated with foal rotavirus, and one of three with human rotavirus, were protected against bovine rotavirus challenge. Pr...
Ishihara A, Zekas LJ, Litsky AS, Weisbrode SE, Bertone AL.This study evaluated healing of equine metacarpal/metatarsal osteotomies in response to percutaneous injection of autologous dermal fibroblasts (DFbs) genetically engineered to secrete bone morphogenetic protein-2 (BMP2) or demonstrate green fluorescent protein (GFP) gene expression administered 14 days after surgery. Radiographic assessment of bone formation indicated greater and earlier healing of bone defects treated with DFb with BMP2 gene augmentation. Quantitative computed tomography and biomechanical testing revealed greater mineralized callus and torsional strength of DFb-BMP2-treated ...
Lacitignola L, Crovace A, Rossi G, Francioso E.To compare cultured bone marrow mesenchymal cells (cBMSC), bone marrow mononucleated cells (BMMNCs), and placebo to repair collagenase-induced tissue damage in an equine model of experimental tendonitis, 6 Standardbred horses with no signs of previous SDF tendon injury have been recruited. Three weeks after collagenase treatment an average of either 5.5 x 10(6) cBMSCs or 122.3 x 10(6) BMMNCs, saline solution (placebo) or fibrin glue were injected intralesionally in random order. Horses were stall rested for 21 weeks, and tendon ultrasound scans performed before and during this period. Horses w...
Ortved KF, Begum L, Mohammed HO, Nixon AJ.Cartilage injury often precipitates osteoarthritis which has driven research to bolster repair in cartilage impact damage. Autologous chondrocytes transduced with rAAV5-IGF-I were evaluated in chondral defects in a well-established large animal model. Cartilage was harvested from the talus of 24 horses; chondrocytes were isolated and stored frozen. Twenty million cells were cultured and transduced with 10(5) AAV vg/cell prior to implantation. Chondrocytes from eight horses were transduced with rAAV5-IGF-I, chondrocytes from eight horses with rAAV5-GFP, and chondrocytes from eight horses were n...
Skedros JG, Su SC, Bloebaum RD.Artiodactyl and perissodactyl calcanei have been recently introduced as models for examining bone for mechanically mediated adaptation. We have reported substantial regional variations in cortical bone microstructure and mineral content within the same cross-section of mule deer calcanei. In part, these variations may be adaptations accommodating the customary presence of predominantly tension, compression, and shear strain modes in mutually exclusive cortical locations. Calcanei from skeletally mature horses, elk, and sheep were examined in order to corroborate these previous findings. From e...
Chevrier A, Kouao AS, Picard G, Hurtig MB, Buschmann MD.Microfracture repair tissue in young adult humans and in rabbit trochlea is frequently of higher quality than in corresponding ovine or horse models or in the rabbit medial femoral condyle (MFC). This may be related to differences in subchondral properties since repair is initiated from the bone. We tested the hypothesis that subchondral bone from rabbit trochlea and the human MFC are structurally similar. Trochlea and MFC samples from rabbit, sheep, and horse were micro-CT scanned and histoprocessed. Samples were also collected from normal and lesional areas of human MFC. The subchondral bone...
Horohov DW.The modern horse, Equus caballus has historically made important contributions to the field of immunology, dating back to Emil von Behring's description of curative antibodies in equine serum over a century ago. While the horse continues to play an important role in human serotherapy, the mouse has replaced the horse as the predominant experimental animal in immunology research. Nevertheless, continuing efforts have led to an improved understanding of the equine immune response in a variety of infectious and non-infectious diseases. Based on this information, we can begin to identify specific ...
Nixon AJ, Sparks HD, Begum L, McDonough S, Scimeca MS, Moran N, Matthews GL.Autologous chondrocyte implantation (ACI) using a collagen scaffold (matrix-induced ACI; MACI) is a next-generation approach to traditional ACI that provides the benefit of autologous cells and guided tissue regeneration using a biocompatible collagen scaffold. The MACI implant also has inherent advantages including surgical implantation via arthroscopy or miniarthrotomy, the elimination of periosteal harvest, and the use of tissue adhesive in lieu of sutures. This study evaluated the efficacy of the MACI implant in an equine full-thickness cartilage defect model at 1 year. Methods: Autologous...
Turlej RK, Fiévez L, Sandersen CF, Dogné S, Kirschvink N, Lekeux P, Bureau F.As granulocyte/macrophage colony stimulating factor (GM-CSF) mediated delay of granulocyte apoptosis contributes to the accumulation of inflammatory cells at the site of inflammation in many diseases, we sought to determine whether asthma is also associated with a GM-CSF dependent increase in lung granulocyte survival. Moreover, because GM-CSF mediates its effects through activation of signal transducer and activator of transcription 5 (STAT5), we also investigated the potential role of STAT5 in allergic inflammation. Methods: Blood granulocytes were recovered from six healthy and six heaves a...
Bullone M, Beauchamp G, Godbout M, Martin JG, Lavoie JP.Endobronchial ultrasonography (EBUS) revealed differences in the thickness of the layer representing subepithelial tissues (L2) between human asthmatics and controls, but whether this measurement correlates with airway smooth muscle (ASM) remodeling in asthma is unknown. In this study, we sought to determine the ability of EBUS to predict histological ASM remodeling in normal and equine asthmatic airways. We studied 109 isolated bronchi from the lungs of 13 horses. They underwent EBUS examination using a 30 MHz radial probe before being processed for histology. ASM remodeling parameters were e...
Regan DP, Aarnio MC, Davis WS, Carmichael KP, Vandenplas ML, Lauderdale JD, Moore PA.Equine recurrent uveitis (ERU) is a spontaneous disease that is the most common cause of blindness in horses, affecting up to 15% of the horse population. Th17 cells are a major cell population driving the pathogenesis in several mouse models of autoimmune inflammation, including experimental autoimmune uveitis. The purpose of this study is to investigate the role a Th17 cell-mediated response plays in the pathogenesis of ERU. Methods: Banked, Davidson's-fixed equine globes histopathologically diagnosed with ERU (n = 7) were compared immunohistochemically with healthy control globes (n = 7). I...
Galvão AM, Ferreira-Dias G, Skarzynski DJ.In adults, physiological angiogenesis is a rare event, with few exceptions as the vasculogenesis needed for tissue growth and function in female reproductive organs. Particularly in the corpus luteum (CL), regulation of angiogenic process seems to be tightly controlled by opposite actions resultant from the balance between pro- and antiangiogenic factors. It is the extremely rapid sequence of events that determines the dramatic changes on vascular and nonvascular structures, qualifying the CL as a great model for angiogenesis studies. Using the mare CL as a model, reports on locally produced c...
Branly T, Bertoni L, Contentin R, Rakic R, Gomez-Leduc T, Desancé M, Hervieu M, Legendre F, Jacquet S, Audigié F, Denoix JM, Demoor M, Galéra P.Articular cartilage presents a poor capacity for self-repair. Its structure-function are frequently disrupted or damaged upon physical trauma or osteoarthritis in humans. Similar musculoskeletal disorders also affect horses and are the leading cause of poor performance or early retirement of sport- and racehorses. To develop a therapeutic solution for horses, we tested the autologous chondrocyte implantation technique developed on human bone marrow (BM) mesenchymal stem cells (MSCs) on horse BM-MSCs. This technique involves BM-MSC chondrogenesis using a combinatory approach based on the associ...
Spaas JH, Guest DJ, Van de Walle GR.Tendon injuries are one of the most common orthopaedic problems in both human and equine athletes. When a damaged tendon heals naturally, it loses a substantial part of the original strength and elasticity. Therefore, tendons recover structurally (reparation) but not functionally (regeneration) after conservative medical or surgical treatment. Since the structure and matrix composition of human and equine tendons share many similarities, the nature of tendon injuries are also strongly comparable in both species. Therefore, the evaluation of regenerative therapies in horses may have application...
Bullone M, Lavoie JP.Human asthma is a complex and heterogeneous disorder characterized by chronic inflammation, bronchospasm and airway remodeling. The latter is a major determinant of the structure-function relationship of the respiratory system and likely contributes to the progressive and accelerated decline in lung function observed in patients over time. Corticosteroids are the cornerstone of asthma treatment. While their action on inflammation and lung function is well characterized, their effect on remodeling remains largely unknown. An important hindrance to the study of airway remodeling as a major focu...
Boyce MK, Trumble TN, Carlson CS, Groschen DM, Merritt KA, Brown MP.Develop a non-terminal animal model of acute joint injury that demonstrates clinical and morphological evidence of early post-traumatic osteoarthritis (PTOA). Methods: An osteochondral (OC) fragment was created arthroscopically in one metacarpophalangeal (MCP) joint of 11 horses and the contralateral joint was sham operated. Eleven additional horses served as unoperated controls. Every 2 weeks, force plate analysis, flexion response, joint circumference, and synovial effusion scores were recorded. At weeks 0 and 16, radiographs (all horses) and arthroscopic videos (OC injured and sham joints) ...
Turley SM, Thambyah A, Riggs CM, Firth EC, Broom ND.The palmar aspect of the third metacarpal (MC3) condyle of equine athletes is known to be subjected to repetitive overloading that can lead to the accumulation of joint tissue damage, degeneration, and stress fractures, some of which result in catastrophic failure. However, there is still a need to understand at a detailed microstructural level how this damage progresses in the context of the wider joint tissue complex, i.e. the articular surface, the hyaline and calcified cartilage, and the subchondral bone. MC3 bones from non-fractured joints were obtained from the right forelimbs of 16 Thor...
Maninchedda U, Lepage OM, Gangl M, Hilairet S, Remandet B, Meot F, Penarier G, Segard E, Cortez P, Jorgensen C, Steinberg R.The aim of this work was to develop an equine metacarpophalangeal joint model that induces osteoarthritis that is not primarily mediated by instability or inflammation. The study involved six Standardbred horses. Standardized cartilage surface damage or "grooves" were created arthroscopically on the distal dorsal aspect of the lateral and medial metacarpal condyles of a randomly chosen limb. The contralateral limb was sham operated. After 2 weeks of stall rest, horses were trotted 30 minutes every other day for 8 weeks, then evaluated for lameness and radiographed. Synovial fluid was analyzed ...
Hall V, Hinrichs K, Lazzari G, Betts DH, Hyttel P.Over many decades assisted reproductive technologies, including artificial insemination, embryo transfer, in vitro production (IVP) of embryos, cloning by somatic cell nuclear transfer (SCNT), and stem cell culture, have been developed with the aim of refining breeding strategies for improved production and health in animal husbandry. More recently, biomedical applications of these technologies, in particular, SCNT and stem cell culture, have been pursued in domestic mammals in order to create models for human disease and therapy. The following review focuses on presenting important aspects of...
Davies RS, Madigan JE, Hodzic E, Borjesson DL, Dumler JS.Anaplasma phagocytophilum is the zoonotic cause of granulocytic anaplasmosis. We hypothesized that immune response, specifically gamma interferon (IFN-γ), plays a role in disease severity. To test this, horses were infected and IFNG expression was pharmacologically downregulated using corticosteroids. Eight horses were infected with A. phagocytophilum; 4 received dexamethasone on days 4 to 8 of infection. Clinical signs, hematologic parameters, and transcription of cytokine/chemokine genes were compared among treated and untreated horses. Infection was quantitated by msp2 real-time PCR and mi...
Bice DE, Seagrave J, Green FH.Asthma is now recognized to be a chronic inflammatory disease that affects the whole lung. Incidence appears to be increasing despite improved treatment regimens. There is substantial epidemiological evidence suggesting a relationship between the incidence and severity of asthma (e.g., hospitalizations) and exposure to increased levels of air pollution, especially fine and ultrafine particulate material, in susceptible individuals. There have been a few studies in animal models that support this concept, but additional animal studies to test this hypothesis are needed. However, such studies mu...
