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.
Zanotto GM, Liesbeny P, Barrett M, Zlotnick H, Frank E, Grodzinsky AJ, Frisbie DD.Microfracture augmentation can be a cost-effective single-step alternative to current cartilage repair techniques. Trypsin pretreatment combined with a growth factor-functionalized self-assembling KLD hydrogel ("functionalized hydrogel") has been shown to improve overall cartilage repair and integration to surrounding tissue in small animal models of osteochondral defects. Microfracture combined with trypsin treatment and a functionalized hydrogel will improve reparative tissue quality and integration as compared with microfracture alone in an equine model. Controlled laboratory study. Bilater...
Tanaka Y, Suganuma K, Watanabe K, Kobayashi Y.Dourine, caused by infection with Trypanosoma equiperdum, is one of the trypanosomiasis in equids. The clinical course of dourine is long-term, ranging from 1-2 months to several years. Since the pathogenesis of dourine has not yet been elucidated, experimental studies using mouse infection models are needed. Although mice are not susceptible to most T. equiperdum strains, some strains can infect mice. Even in such strains, infected mice develop rapidly transient parasitemia and die within 2-8 days. Therefore, mice experimentally infected with these T. equiperdum strains are not suitable for m...
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...
Tomlinson JE, Wolfisberg R, Fahnøe U, Patel RS, Trivedi S, Kumar A, Sharma H, Nielsen L, McDonough SP, Bukh J, Tennant BC, Kapoor A, Rosenberg BR....Equine hepacivirus (EqHV) is phylogenetically the closest relative of HCV and shares genome organization, hepatotropism, transient or persistent infection outcome, and the ability to cause hepatitis. Thus, EqHV studies are important to understand equine liver disease and further as an outbred surrogate animal model for HCV pathogenesis and protective immune responses. Here, we aimed to characterize the course of EqHV infection and associated protective immune responses. Seven horses were experimentally inoculated with EqHV, monitored for 6 months, and rechallenged with the same and, subsequen...
Johnson SA, Valdés-Martínez A, Turk PJ, Wayne McIlwraith C, Barrett MF, McGilvray KC, Frisbie DD.The range of diagnostic modalities available to evaluate superficial digital flexor tendon (SDFT) injury includes magnetic resonance imaging (MRI), computed tomography (CT) and ultrasonography (US). Direct, comprehensive comparison of multi-modality imaging characteristics to end-point data has not previously been performed using a model of tendinopathy but is required to obtain a better understanding of each modality's diagnostic capabilities. Objective: To compare CT, MRI and US evaluation to outcome measures for histologic, biochemical and biomechanical parameters using an equine surgical m...
Patterson Rosa L, Walker N, Mallicote M, MacKay RJ, Brooks SA.Similar to humans, the horse relies predominantly on the evaporation of sweat from the skin surface to dissipate excess body heat. Loss of the sweat response or anhidrosis can result in life-threatening hyperthermia. Anhidrosis occurs more frequently in some breeds as well as occurs at an increased frequency among individuals with a family history, suggesting a heritable component to the pathology. Given the natural occurrence and indications of genetic components in the etiology, we utilized genomics to better understand the molecular mechanisms involved in sweat response. We performed a case...
Bardin AL, Tang L, Panizzi L, Rogers CW, Colborne GR.Musculoskeletal injuries in horses are the main cause of retirement, rest, and death. To understand these injuries, it is necessary to study loads in muscles, tendons and ligaments. A musculoskeletal model makes it possible to consider all structures simultaneously and avoids invasive measurements. At present, most computational models of the equine limb described in the literature have been limited to the distal limb. The aim of this study was to create a preliminary musculoskeletal model of the whole equine forelimb and to run it with kinematic data collected during gait. The model was devel...
Villarraza CJ, Antuña S, Tardivo MB, Rodríguez MC, Mussio P, Cattaneo L, Fontana D, Díaz PU, Ortega HH, Tríbulo A, Macagno A, Bó GA, Ceaglio N....Equine chorionic gonadotropin (eCG) is a heterodimeric glycoprotein hormone produced by pregnant mares that has been used to improve reproductive performance in different domestic species. Several strategies to produce the hormone in a recombinant way have been reported; nevertheless, no approach has been able to produce a recombinant eCG (reCG) with significant in vivo bioactivity or in sufficient quantities for commercial purposes. For this reason, the only current product available on the market consists of partially purified preparations from serum of pregnant mares (PMSG). Herein, we des...
Otto S, Michler JK, Dhein S, Mülling CKW.Distal axonopathy is seen in a broad range of species including equine patients. In horses, this degenerative disorder of the recurrent laryngeal nerve is described as recurrent laryngeal neuropathy (RLN). The dysfunctional innervation of the cricoarytenoideus dorsalis muscle (CAD) leads to a loss of performance in affected horses. In general, ex vivo models of the larynx are rare and for equine patients, just one short report is available. To allow for testing new therapy approaches in an isolated organ model, we examined equine larynges in a constant pressure perfused setup. In order to chec...
Turlo AJ, McDermott BT, Barr ED, Riggs CM, Boyde A, Pinchbeck GL, Clegg PD.Osteoarthritis (OA) is a disease of the entire joint but the relationship between pathological events in various joint tissues is poorly understood. We examined concurrent changes in bone, cartilage, and synovium in a naturally occurring equine model of joint degeneration. Joints (n = 64) were grossly assessed for palmar/plantar osteochondral disease (POD) in racehorses that required euthanasia for unrelated reasons and assigned a grade of 0 (n = 34), 1 (n = 17), 2 or 3 (n = 13) using a recognized grading scheme. Synovium, cartilage, and subchondral bone were collected for hist...
Saukko AEA, Nykänen O, Sarin JK, Nissi MJ, Te Moller NCR, Weinans H, Mancini IAD, Visser J, Brommer H, van Weeren PR, Malda J, Grinstaff MW....To prevent the progression of posttraumatic osteoarthritis, assessment of cartilage composition is critical for effective treatment planning. Posttraumatic changes include proteoglycan (PG) loss and elevated water content. Quantitative dual-energy computed tomography (QDECT) provides a means to diagnose these changes. Here, we determine the potential of QDECT to evaluate tissue quality surrounding cartilage lesions in an equine model, hypothesizing that QDECT allows detection of posttraumatic degeneration by providing quantitative information on PG and water contents based on the partitions of...
Larson EM, Wagner B.Horses have many naturally occurring diseases that mimic similar conditions in humans. The ability to conduct environmentally controlled experiments and induced disease studies in a genetically diverse host makes the horse a valuable intermediate model between mouse studies and human clinical trials. This review highlights important similarities in the immune landscape between horses and humans using current research on two equine diseases as examples. First, equine herpesvirus type 1 (EHV-1) infection initiates a series of innate inflammatory signals at its mucosal entry site in the upper res...
Larson EM, Babasyan S, Wagner B.IL-8 is a potent chemokine that recruits neutrophils and basophils to promote inflammation in many species. IL-8 is produced by many cell types, including monocytes. In this study, we report a novel role for IgE-binding monocytes, a rare peripheral immune cell type, to promote allergic inflammation through IL-8 production in a horse model of natural IgE-mediated allergy. We developed a mAb with confirmed specificity for both recombinant and native equine IL-8 for flow cytometric analysis. Equine IL-8 was produced by CD14/MHC class II/CD16 monocytes, including a subpopulation of IgE-binding mon...
Della Tommasa S, Winter K, Seeger J, Spitzbarth I, Brehm W, Troillet A.Horses are a widely accepted model for osteoarthritis (OA) research. Synovial tissue sampling is commonly used in studies to evaluate and grade the progress of OA or to assess treatment effects. Synovial explants play an important role in ex-vivo studies, increasingly replacing the use of living animals. To understand histomorphological changes in the process of joint-related diseases such as OA, detailed information about histomorphometric parameters of unaffected synovial villi is necessary. The objective of the present study was to evaluate the mean width of the intimal synovial lining and ...
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...
Naumann S, Meyer JP, Kiesow A, Mrestani Y, Wohlrab J, Neubert RH.The penetration behavior into human nails and animal hoof membranes of a novel antifungal agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentratio...
Pereyra-Bonnet F, Fernández-Martín R, Olivera R, Jarazo J, Vichera G, Gibbons A, Salamone D.Transgenesis is an essential tool in many biotechnological applications. Intracytoplasmic sperm injection (ICSI)-mediated gene transfer is a powerful technique to obtain transgenic pups; however, most domestic animal embryos do not develop properly after ICSI. An additional step in the protocol, namely assistance by haploid chemical activation, permits the use of ICSI-mediated gene transfer to generate transgenic preimplantation embryos in a wide range of domestic species, including ovine, porcine, feline, equine and bovine. In the present study, spermatozoa from five species were coincubated ...
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 ...
Murphy BA, Walsh CM, Woodward EM, Prendergast RL, Ryle JP, Fallon LH, Troedsson MH.Artificial lighting is commonly used to advance the breeding season in horses. Light masks have been developed that direct light at a single eye to inhibit the production of melatonin, the decoder of photoperiod for seasonally breeding animals. Objective: To investigate whether low-intensity blue light from light masks was effective at advancing the breeding season in mares. Methods: Controlled experiment. Methods: Data on reproductive activity was collected from 3 groups of mares maintained on Kentucky horse farms under various lighting conditions between 20 November 2011 and 10 February 2012...
Tozaki T, Gamo S, Takasu M, Kikuchi M, Kakoi H, Hirota KI, Kusano K, Nagata SI.Doping control is an important and indispensable aspect of fair horse racing; genetic doping has been recently included to this. In this study, we aimed to develop a detection method of gene doping. A plasmid cloned with human erythropoietin gene (p.hEPO, 250 μg/head) was intramuscularly injected into a microminipig. Subsequently, p.hEPO was extracted from 1 mL of plasma and detected by droplet digital polymerase chain reaction. Results: The results confirmed that the maximum amount of plasmid was detected at 15 min after administration and the majority of the plasmid was degraded in the b...
Mohammed HO, Divers TJ, Summers BA, de Lahunta A.Equine motor neuron disease (EMND) is a spontaneous neurologic disorder of adult horses which results from the degeneration of motor neurons in the spinal cord and brain stem. Clinical manifestations, pathological findings, and epidemiologic attributes resemble those of human motor neuron disease (MND). As in MND the etiology of the disease is not known. We evaluated the predisposition role of vitamin E deficiency on the risk of EMND. Methods: Eleven horses at risk of EMND were identified and enrolled in a field trial at different times. The horses were maintained on a diet deficient in vitami...
Celeste CJ, Deschesne K, Riley CB, Theoret CL.To map skin temperature kinetics, and by extension skin blood flow throughout normal or abnormal repair of full-thickness cutaneous wounds created on the horse body and limb, using infrared thermography. Methods: Experimental. Methods: Standardbreds (n = 6), aged 3-4 years. Methods: Three cutaneous wounds were created on the dorsolateral surface of each metacarpus and on the lateral thoracic wall. Thoracic skin wounds and those on 1 randomly chosen forelimb healed by second intention without a bandage, whereas contralateral limb wounds were bandaged to induce formation of exuberant granulation...
Rotter Sopasakis V, Wickelgren R, Sukonina V, Brantsing C, Svala E, Hansson E, Enerbäck S, Lindahl A, Skiöldebrand E.Chondrocytes are responsible for remodeling and maintaining the structural and functional integrity of the cartilage extracellular matrix. Because of the absence of a vascular supply, chondrocytes survive in a relatively hypoxic environment and thus have limited regenerative capacity during conditions of cellular stress associated with inflammation and matrix degradation, such as osteoarthritis (OA). Glucose is essential to sustain chondrocyte metabolism and is a precursor for key matrix components. In this study, we investigated the importance of glucose as a fuel source for matrix repair dur...
Mitchell A, Rivas KA, Smith R, Watts AE.Equine superficial digital flexor tendon injury is a well-accepted model of human tendon injury and is routinely treated with local injections of autologous mesenchymal stem cells (MSCs). Identification of a clinically safe medium for short-term cryopreservation of MSCs prior to cell implantation would streamline laboratory and clinical procedures for autologous regenerative therapies. Veterinary experience with short-term (MSCs prepared after the injury has occurred) cryopreserved MSCs in naturally occurring injury in the horse will be of value to human practitioners. Methods: Equine bone mar...
Chiaradia E, Pepe M, Tartaglia M, Scoppetta F, D'Ambrosio C, Renzone G, Avellini L, Moriconi F, Gaiti A, Bertuglia A, Beccati F, Scaloni A.Osteoarthritis (OA) and osteochondrosis (OC) are two of the main challenges in orthopedics, whose definitive diagnosis is usually based on radiographic/arthroscopic evidences. Their early diagnosis should allow preventive or timely therapeutic actions, which are generally precluded from the poor relationships occurring between symptomatologic and radiographic evidences. These limitations should be overcome by improving the knowledge on articular tissue metabolism and on molecular factors regulating its normal homeostasis, also identifying novel OA and OC biomarkers suitable for their earlier d...
Alves KA, Alves BG, Gastal GD, de Tarso SG, Gastal MO, Figueiredo JR, Gambarini ML, Gastal EL.Ovarian tissue collected by biopsy procedures allows the performance of many studies with clinical applications in the field of female fertility preservation. The aim of the present study was to investigate the influence of reproductive phase (anestrous vs. diestrous) and ovarian structures (antral follicles and corpus luteum) on the quality, class distribution, number, and density of preantral follicles, and stromal cell density. Ovarian fragments were harvested by biopsy pick-up procedures from mares and submitted to histological analysis. The mean preantral follicle and ovarian stromal cell...
Rakic R, Bourdon B, Demoor M, Maddens S, Saulnier N, Galéra P.Umbilical cord blood mesenchymal stromal/stem cells (UCB-MSCs) and umbilical cord matrix MSCs (UCM-MSCs) have chondrogenic potential and are alternative sources to standard surgically derived bone marrow or adipose tissue collection for cartilage engineering. However, the majority of comparative studies explore neonatal MSCs potential only on ISCT benchmark assays accounting for some bias in the reproducibility between in vitro and in clinical studies. Therefore, we characterized equine UCB-MSCs and UCM-MSCs and investigated with particular attention their chondrogenesis potential in 3D cultu...
Esteves CL, Donadeu FX.The discovery that pericytes are in vivo counterparts of Mesenchymal Stem/Stromal Cells (MSCs) has placed these perivascular cells in the research spotlight, bringing up hope for a well-characterized cell source for clinical applications, alternative to poorly defined, heterogeneous MSCs preparations currently in use. Native pericytes express typical MSC markers and, after isolation by fluorescence-activated cell sorting, display an MSC phenotype in culture. These features have been demonstrated in different species, including humans and horses, the main targets of regenerative treatments. Sig...
McCabe L, Griffin LD, Kinzer A, Chandler M, Beckwith JB, McCabe ER.The lethal white foal syndrome (LWFS) is a congenital abnormality of overo spotted horses which is a model for human aganglionic megacolon or Hirschsprung disease. Foals with LWFS have an all white, or nearly all white, coat. They also present clinically with an intestinal obstruction that proves fatal within the first few days of life. The LWFS involves both melanocytes and intestinal ganglion cells, and appears to result from a genetic defect involving neural crest cells. This report describes pathologic studies of two recent cases of LWFS. Two different hypothetical models of inheritance of...
Cadby JA, David F, van de Lest C, Bosch G, van Weeren PR, Snedeker JG, van Schie HT.Injuries in energy-storing tendons are common in both horses and man. The high prevalence of reinjury and the relatively poor prognosis for returning to preinjury performance levels warrant further research, for which well characterised models would be very helpful. Objective: Given the clinical similarities in tendinopathy of energy-storing tendons, we hypothesised that a recently developed experimental model of equine tendon injury would display many of the characteristics of clinical tendinopathy and could therefore be of use for both species, thus providing comparative insight to the human...
Kim B, Yoon JH, Zhang J, Eric Mueller PO, Halper J.Defects in glycosylation of decorin can result in systemic hereditary disease. A mutation in the galactosyl transferase I gene is the underlying defect of a progeroid form of Ehlers-Danlos syndrome. We have previously described pathological changes in equine systemic proteoglycan accumulation (ESPA, formerly degenerative suspensory ligament desmitis) as consisting of excessive presence of decorin and other proteoglycans in organs and structures with a high content of connective tissue. Using liquid chromatography/mass spectrometry, and one- and two-dimensional immunoblotting we have determined...
Hodavance MS, Ralston SL, Pelczer I.Metabonomic analysis is a powerful tool for identifying and characterizing metabolic disorders, for example type 2 diabetes and the metabolic syndrome. Nuclear magnetic resonance (NMR) spectroscopy is an essential tool for such analysis, with special benefits. The review assesses the current status and potential of NMR-based metabonomics of type 2 diabetes. The horse is proposed as a possible model for studying this condition and disease. Some examples are shown of horse blood analyses by NMR.
Zou X, Zou L, Foldager C, Bendtsen M, Feng W, Bünger CE.To elucidate the molecular mechanisms of spinal fusion with different graft materials during an anterior lumbar interbody fusion, we examined the gene-expression profiles after implantation of equine bone protein extract, rhBMP-2 and autograft using microarray technology and data analysis, including hierarchical clustering, self-organizing maps (SOM), KEGG pathway and Biological process GO analyses in a porcine model. The results suggest that equine bone protein extract exhibited a more similar expression pattern with autograft than that of rhBMP-2. rhBMP-2 recruits progenitor cells, prolifera...
Zayed M, Newby S, Misk N, Donnell R, Dhar M.Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from t...
Karagianni AE, Lisowski ZM, Hume DA, Scott Pirie R.The mononuclear phagocyte system (MPS) is a family of cells of related function that includes bone marrow progenitors, blood monocytes and resident tissue macrophages. Macrophages are effector cells in both innate and acquired immunity. They are a major resident cell population in every organ and their numbers increase in response to proinflammatory stimuli. Their function is highly regulated by a wide range of agonists, including lymphokines, cytokines and products of microorganisms. Macrophage biology has been studied most extensively in mice, yet direct comparisons of rodent and human macro...
Ginther OJ.The mare is a good comparative model for study of ovarian follicles in women, owing to striking similarities in follicular waves and the mechanism for selection of a dominant follicle. Commonality in follicle dynamics between mares and women include: (1) a ratio of 2.2:1 (mare:woman) in diameter of the largest follicle at wave emergence when the wave-stimulating FSH surge reaches maximum, in diameter increase of the two largest follicles between emergence and the beginning of deviation between the future dominant and subordinate follicles, in diameter of each of the two largest follicles at th...
Kim H, Lee T, Park W, Lee JW, Kim J, Lee BY, Ahn H, Moon S, Cho S, Do KT, Kim HS, Lee HK, Lee CK, Kong HS, Yang YM, Park J, Kim HM, Kim BC, Hwang S....The modern horse (Equus caballus) is the product of over 50 million yrs of evolution. The athletic abilities of the horse have been enhanced during the past 6000 yrs under domestication. Therefore, the horse serves as a valuable model to understand the physiology and molecular mechanisms of adaptive responses to exercise. The structure and function of skeletal muscle show remarkable plasticity to the physical and metabolic challenges following exercise. Here, we reveal an evolutionary layer of responsiveness to exercise-stress in the skeletal muscle of the racing horse. We analysed differentia...
Fink MK, Giuliano EA, Tandon A, Mohan RR.To evaluate the safety and efficacy of Pirfenidone (PFD) in the treatment of equine corneal fibrosis using an in vitro model. Methods: Healthy donor equine corneas were collected and used to generate primary equine corneal fibroblasts (ECFs) by growing cultures in minimal essential medium supplemented with 10% fetal bovine serum. Equine corneal myofibroblasts (ECMs), used as a model of equine corneal fibrosis, were produced by growing ECF cultures in serum-free medium containing transforming growth factor β1 (1 ng/mL). Trypan blue viability assays and changes in ECF morphology were utilized t...
Hammond SA, Cook SJ, Falo LD, Issel CJ, Montelaro RC.Immunization regimens that induce a broadly reactive cytolytic T lymphocyte (CTL) response specific for lentiviral antigens have emerged as the leading candidates in efficacy trials conducted in both animal modelshumans. To date, lentivirus vaccination strategies have overlooked one such immunization strategy, namely the use of particulate antigens. To evaluate the efficacy of targeting antigen into the phagocytic pathway to elicit a cell-mediated immune response to lentiviral antigens, we initiated the first study of a particulate-based vaccination protocol using a large animal model system. ...
Korthagen NM, Brommer H, Hermsen G, Plomp SGM, Melsom G, Coeleveld K, Mastbergen SC, Weinans H, van Buul W, van Weeren PR.Cartilage repair remains a major challenge and treatment of (osteo)chondral defects generally results in poor quality fibrous repair tissue. Our approach aims to address some of the major biomechanical issues encountered in scaffold-based cartilage repair, such as insufficient stiffness of the scaffolds, step formation at the interface with the native tissue and inadequate integration with the original tissue. Two osteochondral defects were created on the medial femoral trochlear ridge in each stifle of six Shetland ponies. The defects were filled with a bi-layered implant consisting of a poly...
Burk J, Badylak SF, Kelly J, Brehm W.Pioneering clinical stem cell research is being performed in the horse, a recipient of cutting edge veterinary medicine as well as a unique animal model, paving the way for human medical applications. Although demonstrable progress has been made on the clinical front, in vitro characterization of equine stem cells is still in comparatively early stages. To translate the promising results of clinical stem cell therapy in the horse, advances must be made in the characterization of equine stem cells. Aiming to improve communication between veterinarians and other natural scientists, this review g...
Daly JM, Yates RJ, Browse G, Swann Z, Newton JR, Jessett D, Davis-Poynter N, Mumford JA.Vaccination and challenge studies in ponies are the most relevant experimental system for predicting whether strains included in equine influenza vaccines are relevant, but they are difficult to perform. Objective: In order to investigate the feasibility of using a small animal model, results of a cross-protection study in hamsters were compared with those from a previous pony challenge experiment. Methods: Animals were immunised with inactivated vaccines containing one of 4 strains of equine influenza A H3N8 subtype virus isolated over a 26 year period (1963 to 1989), then challenged with a 1...
Merkens HW, Schamhardt HC.Force plate data from walking horses were used to evaluate the locomotion of a group of six horses during experimentally induced lameness in a forelimb or a hindlimb. By tightening or loosening screws in modified horseshoes the resulting pressure pain on the sole enabled induction and release of three different degrees of supporting lameness within a period of 2 h. The ground reaction force (GRF) patterns of the different recording sessions were compared with control data of the same horse as well as with the 'standard' horse data using a quantitative evaluation procedure involving 93 GRF para...
Kajabi AW, Casula V, Sarin JK, Ketola JH, Nykänen O, Te Moller NCR, Mancini IAD, Visser J, Brommer H, René van Weeren P, Malda J, Töyräs J....Chondral lesions lead to degenerative changes in the surrounding cartilage tissue, increasing the risk of developing post-traumatic osteoarthritis (PTOA). This study aimed to investigate the feasibility of quantitative magnetic resonance imaging (qMRI) for evaluation of articular cartilage in PTOA. Articular explants containing surgically induced and repaired chondral lesions were obtained from the stifle joints of seven Shetland ponies (14 samples). Three age-matched nonoperated ponies served as controls (six samples). The samples were imaged at 9.4 T. The measured qMRI parameters included ...
Tomlinson JE, Wolfisberg R, Fahnøe U, Patel RS, Trivedi S, Kumar A, Sharma H, Nielsen L, McDonough SP, Bukh J, Tennant BC, Kapoor A, Rosenberg BR....Equine hepacivirus (EqHV) is phylogenetically the closest relative of HCV and shares genome organization, hepatotropism, transient or persistent infection outcome, and the ability to cause hepatitis. Thus, EqHV studies are important to understand equine liver disease and further as an outbred surrogate animal model for HCV pathogenesis and protective immune responses. Here, we aimed to characterize the course of EqHV infection and associated protective immune responses. Seven horses were experimentally inoculated with EqHV, monitored for 6 months, and rechallenged with the same and, subsequen...
