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.
Storgaard IH, Kristensen J, Larsen C, Mertz N, Østergaard J, Larsen SW.Intra-articular depot injectables based on in situ suspension formation of ester prodrugs of nonsteroidal anti-inflammatory drugs are promising for management of joint pain. As candidates for this delivery approach, 5 diclofenac ester prodrugs comprising different imidazole-containing promoieties were synthesized and their physicochemical properties characterized. In vitro hydrolysis rates were investigated in buffer solutions, in 40% (v/v) human, equine, canine, and rat plasma, and in 80% (v/v) human and equine synovial fluid. Bioconversion of the prodrugs to diclofenac was found to be enzym...
Bond SL, Workentine M, Hundt J, Gilkerson JR, Léguillette R.Prolonged exposure to environmental antigens or allergens elicits an immune response in both healthy horses and those with mild asthma. Corticosteroids often are used to treat lower airway inflammation. Objective: To investigate the changes in equine herpesvirus (EHV)-1,2,4,5 glycoprotein B gene expression and changes in respiratory bacterial and fungal communities after nebulized dexamethasone treatment of horses with asthma. Methods: Horses with naturally occurring mild asthma (n = 16) and healthy control horses (n = 4). Methods: Prospective, randomized, controlled, blinded clinical trial. P...
Draper ACE, Wilson Z, Maile C, Faccenda D, Campanella M, Piercy RJ.A glutamic acid to lysine (E40K) residue substitution in superoxide dismutase 1 (SOD1) is associated with canine degenerative myelopathy: the only naturally occurring large animal model of amyotrophic lateral sclerosis (ALS). The E40 residue is highly conserved across mammals, except the horse, which naturally carries the (dog mutant) K40 residue. Here we hypothesized that in vitro expression of mutant dog SOD1 would recapitulate features of human ALS (ie, SOD1 protein aggregation, reduced cell viability, perturbations in mitochondrial morphology and membrane potential, reduced ATP production,...
Rodríguez MB, Gambini A, Clérico G, Ynsaurralde-Rivolta AE, Briski O, Largel H, Sansinena M, Salamone DF.Assisted reproduction techniques (ARTs) have become widespread in the equine breeding industry. In particular, the combination of oocyte recovery from live mares followed by IVM and intracytoplasmic sperm injection (ICSI) has increased markedly among the ARTs used with valuable or low-fertility animals. There is currently no consensus among research groups regarding the optimal oocyte maturation period to produce high-quality embryos. In this study, we report the maturation dynamics of equine oocytes at different time points, from 20 to 40h (Experiment 1). In addition, in Experiment 2, equine ...
Peña FJ, O'Flaherty C, Ortiz Rodríguez JM, Martín Cano FE, Gaitskell-Phillips GL, Gil MC, Ortega Ferrusola C.Redox regulation and oxidative stress have become areas of major interest in spermatology. Alteration of redox homeostasis is recognized as a significant cause of male factor infertility and is behind the damage that spermatozoa experience after freezing and thawing or conservation in a liquid state. While for a long time, oxidative stress was just considered an overproduction of reactive oxygen species, nowadays it is considered as a consequence of redox deregulation. Many essential aspects of spermatozoa functionality are redox regulated, with reversible oxidation of thiols in cysteine resid...
Loux SC, Dini P, El-Sheikh Ali H, Kalbfleisch T, Ball BA.The placenta is a dynamic organ which undergoes extensive remodeling throughout pregnancy to support, protect and nourish the developing fetus. Despite the importance of the placenta, very little is known about its gene expression beyond very early pregnancy and post-partum. Therefore, we utilized RNA-sequencing to characterize the transcriptome from the fetal (chorioallantois) and maternal (endometrium) components of the placenta from mares throughout gestation (4, 6, 10, 11 m). Within the endometrium, 47% of genes changed throughout pregnancy, while in the chorioallantois, 29% of genes under...
Abs V, Bonicelli J, Kacza J, Zizzadoro C, Abraham G.Interaction between epithelial cells and fibroblasts play a key role in wound repair and remodelling in the asthmatic airway epithelium. We present the establishment of a co-culture model using primary equine bronchial epithelial cells (EBECs) and equine bronchial fibroblasts (EBFs). EBFs at passage between 4 and 8 were seeded on the bottom of 24-well plates and treated with mitomycin C at 80% confluency. Then, freshly isolated (P0) or passaged (P1) EBECs were seeded on the upper surface of membrane inserts that had been placed inside the EBF-containing well plates and grown first under liquid...
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...
Unterköfler MS, McGorum BC, Milne EM, Licka TF.In horses a number of small intestinal diseases is potentially life threatening. Among them are Equine Grass Sickness (EGS), which is characterised by enteric neurodegeneration of unknown aetiology, as well as reperfusion injury of ischaemic intestine (I/R), and post-operative ileus (POI), common after colic surgery. The perfusion of isolated organs is successfully used to minimize animal testing for the study of pathophysiology in other scenarios. However, extracorporeal perfusion of equine ileum sourced from horses slaughtered for meat production has not yet been described. Therefore the pre...
Menarim BC, Gillis KH, Oliver A, Mason C, Ngo Y, Werre SR, Barrett SH, Luo X, Byron CR, Dahlgren LA.Osteoarthritis (OA) is characterized by macrophage-driven synovitis. Macrophages promote synovial health but become inflammatory when their regulatory functions are overwhelmed. Bone marrow mononuclear cells (BMNCs) are a rich source of macrophage progenitors used for treating chronic inflammation and produce essential molecules for cartilage metabolism. This study investigated the response to autologous BMNC injection in normal and inflamed joints. Synovitis was induced in both radiocarpal joints of 6 horses. After 8 h, 1 inflamed radiocarpal and 1 normal tarsocrural joint received BMNC injec...
Hesselkilde EZ, Carstensen H, Flethøj M, Fenner M, Kruse DD, Sattler SM, Tfelt-Hansen J, Pehrson S, Braunstein TH, Carlson J, Platonov PG....Large animal models are important in atrial fibrillation (AF) research, as they can be used to study the pathophysiology of AF and new therapeutic approaches. Unlike other animal models, horses spontaneously develop AF and could therefore serve as a bona fide model in AF research. We therefore aimed to study the electrical, functional and structural remodelling caused by chronic AF in a horse model. Nine female horses were included in the study, with six horses tachypaced into self-sustained AF and three that served as a time-matched sham-operated control group. Acceleration in atrial fibrilla...
Damasceno Teixeira TV, Fry RC, McKinnon A, Fry KL, Kelly JM, Verma PJ, Burden C, Salamone DF, Gambini A.Epigenetic perturbations during the reprogramming process have been described as the primary cause of the low efficiency of somatic cell nuclear transfer (SCNT). In this study, we tested three strategies targeting nuclear reprogramming to investigate effects on equine SCNT. First, we evaluated the effect of treating somatic cells with chetomin, a fungal secondary metabolite reported to inhibit the trimethylation on histone 3 lysine 9 (H3K9 me3). Second, caffeine was added to the culture medium during the enucleation of oocytes and before activation of reconstructed embryos as a protein phospha...
Johnson PJ, Janvier V, Luh WM, FitzMaurice M, Southard T, Barry EF.There is growing interest in the horse for behavioral, neuroanatomic and neuroscientific research due to its large and complex brain, cognitive abilities and long lifespan making it neurologically interesting and a potential large animal model for several neuropsychological diseases. Magnetic resonance imaging (MRI) is a powerful neuroscientific research tool that can be performed , with adapted equine facilities, or in the research setting. The brain atlas is a fundamental resource for neuroimaging research, and have been created for a multitude animal models, however, none currently exist f...
Ishak GMA, Dutra GA, Gastal GDA, Gastal MO, Feugang JM, Gastal EL.The inability to obtain in vivo samples of antral follicle wall layers without removing the ovaries or sacrificing the animals has limited more in-depth studies on folliculogenesis. In this study, a novel ultrasound-guided follicle wall biopsy (FWB) technique was used to obtain in vivo follicle wall layers and follicular fluid samples of growing antral follicles. The expression of proliferative, hormonal, angiogenic, and pro-/antiapoptotic receptors and proteins in the follicular wall among three follicle classes were compared during the spring transitional anovulatory (SAN) and spring ovulato...
Mazzotti E, Teti G, Falconi M, Chiarini F, Barboni B, Mazzotti A, Muttini A.Osteoarthritis is a degenerative disease that strongly correlates with age and promotes the breakdown of joint cartilage and subchondral bone. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stromal cells (MSCs) isolated from adult tissues. It seems that MSCs derived from synovial joint tissues exhibit superior chondrogenic ability, but their unclear distribution and low frequency actually limit their clinical application. To date, the influence of aging on synovial joint derived MSCs' biological characteristics and differen...
Chung MJ, Park S, Son JY, Lee JY, Yun HH, Lee EJ, Lee EM, Cho GJ, Lee S, Park HS, Jeong KS.In previous work, we established an equine induced pluripotent stem cell line (E-iPSCs) from equine adipose-derived stem cells (ASCs) using a lentiviral vector encoding four transcription factors: Oct4, Sox2, Klf4, and c-Myc. In the current study, we attempted to differentiate these established E-iPSCs into mesenchymal stem cells (MSCs) by serial passaging using MSC-defined media for stem cell expansion. Differentiation of the MSCs was confirmed by analyzing expression levels of the MSC surface markers CD44 and CD29, and the pluripotency markers Nanog and Oct4. Results indicated that the E-iPS...
Hausberger M, Stomp M, Sankey C, Brajon S, Lunel C, Henry S.Research in cognitive psychology has repeatedly shown how much cognition and emotions are mutually related to one another. Psychological disorders are associated with cognitive (attention, memory and judgment) biases and chronic pain may affect attention, learning or memory. Laboratory studies have provided useful insights about the processes involved but observations about spontaneous animal models, living in different stress/welfare conditions may help understand further how cognition and welfare are interrelated in the « real world ». Domestic horses constitute such a model as they live i...
Rogers CW, Dittmer KE.In mammals, play behaviour appears innate and, because of this, may provide insight into the frequency and intensity of load that is required to stimulate positive musculoskeletal development. The objective of this review was to explore the interaction between play and tissue (bone) development at a molecular through to whole-animal level, with specific focus on the horse as a model. The basis of our understanding of the response of bone to loading is the mechanostat theorem. This assumes that at a tissue level, bone attempts to keep localised strain within the physiological range of 1500-2500...
Denham J, Stevenson K, Denham MM.Telomeres are genetically conserved repetitive terminal DNA that protect against genomic instability and shorten with ageing. Here, we reveal the leukocyte telomere length of Equus caballus by measuring terminal restriction fragments (TRFs) using Southern Blot analysis in a cohort of 43 Thoroughbred horses (age: 24 h-25 years). Heterogeneous TRFs were observed in each animal and large inter-animal variation in mean TRF was observed (range: 10.5-18.7 kbp). Mean TRFs were inversely correlated with age (r = -0.47). The estimated yearly rate of telomere attrition was 134 bp. Horses shoul...
Sarin JK, Torniainen J, Prakash M, Rieppo L, Afara IO, Töyräs J.Near infrared (NIR) spectroscopy is a well-established technique that is widely employed in agriculture, chemometrics, and pharmaceutical engineering. Recently, the technique has shown potential in clinical orthopaedic applications, for example, assisting in the diagnosis of various knee-related diseases (e.g., osteoarthritis) and their pathologies. NIR spectroscopy (NIRS) could be especially useful for determining the integrity and condition of articular cartilage, as the current arthroscopic diagnostics is subjective and unreliable. In this work, we present an extensive dataset of NIRS meas...
Jørgensen E, Bay L, Skovgaard LT, Bjarnsholt T, Jacobsen S.Objective: Relevant animal models to study effects of bacterial aggregates on wound healing are lacking. We aimed at establishing an equine wound model with bacterial aggregates to investigate the impact of bacterial inoculation on normal (thorax) and impaired (limb) wound healing. Approach: Wounds were created on three limbs and both thorax sides of six horses. Twelve out of 20 wounds per horse were inoculated with 104 Staphylococcus aureus and 105 Pseudomonas aeruginosa on day 4. Healing was monitored until day 27 by clinical assessment, including wound scoring, surface pH measurements, and ...
Vera L, Campos Arias D, Muylle S, Stergiopulos N, Segers P, van Loon G.Arterial rupture in horses has been observed during exercise, after phenylephrine administration or during parturition (uterine artery). In human pathophysiological research, the use of computer models for studying arterial hemodynamics and understanding normal and abnormal characteristics of arterial pressure and flow waveforms is very common. The objective of this research was to develop a computer model of the equine arterial circulation, in order to study local intra-arterial pressures and flow dynamics in horses. Morphologically, large differences exist between human and equine aortic arc...
Rosser J, Bachmann B, Jordan C, Ribitsch I, Haltmayer E, Gueltekin S, Junttila S, Galik B, Gyenesei A, Haddadi B, Harasek M, Egerbacher M, Ertl P....In this work, we describe a microfluidic three-dimensional (3D) chondrocyte culture mimicking in vivo articular chondrocyte morphology, cell distribution, metabolism, and gene expression. This has been accomplished by establishing a physiologic nutrient diffusion gradient across the simulated matrix, while geometric design constraints of the microchambers drive native-like cellular behavior. Primary equine chondrocytes remained viable for the extended culture time of 3 weeks and maintained the low metabolic activity and high Sox9, aggrecan, and Col2 expression typical of articular chondrocytes...
Gilbertie JM, Schnabel LV, Hickok NJ, Jacob ME, Conlon BP, Shapiro IM, Parvizi J, Schaer TP.Bacterial invasion of synovial joints, as in infectious or septic arthritis, can be difficult to treat in both veterinary and human clinical practice. Biofilms, in the form of free-floating clumps or aggregates, are involved with the pathogenesis of infectious arthritis and periprosthetic joint infection (PJI). Infection of a joint containing an orthopedic implant can additionally complicate these infections due to the presence of adherent biofilms. Because of these biofilm phenotypes, bacteria within these infected joints show increased antimicrobial tolerance even at high antibiotic concentr...
Beaulieu A, Linden AZ, Phillips J, Arroyo LG, Koenig J, Monteith G.In the equine racehorse industry, reduced athletic performance due to joint injury and lameness has been extensively reviewed. Intra-articular injections of glucocorticoids are routinely used to relieve pain and inflammation associated with osteoarthritis. Intra-articular injections of pharmaceutical agents require practice for precise needle placement and to minimize complications. Training on simulators or models is a viable alternative for developing these technical skills. The purpose of this study was to compare the qualitative ultrasonographic characteristics of three-dimensional (3D) pr...
Madigan J, Costa L, Nieves S, Horgan M, Weberg K, Aleman M.Entrapped, stranded and recumbent equids often require emergency rescue. The success of the rescue is often affected by secondary injuries from struggling of the horse to rise and from injury secondary to attempted rescue by pulling on the head or limbs of the equid. Therefore, having ready access to simplified rescue equipment which can be easily applied would be desirable. The devices currently available for these manipulations are not always readily available at the site of an incident. Here, we describe and illustrate the step-by-step use of a Loops System consisting of 183 cm round slings...
Kamel M, Pavulraj S, Osterrieder K, Azab W.Primary infection and pathogenesis of equine herpesvirus type 1 (EHV-1) require an intricate interaction of virus with the mucosal epithelium, mononuclear cells and the vascular endothelium. Studies on EHV-1 have been facilitated by the development of different models that recapitulate the tissue complexity. The available assays can be categorized into (i) models mimicking the epithelium-peripheral blood mononuclear cell (PBMC) interaction, which include mucosal (nasal and vaginal) explants and equine respiratory epithelial cells (EREC) cultures; and (ii) PBMC-endothelium mimicking models,...
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...
McElroy A, Rashmir A, Manfredi J, Sledge D, Carr E, Stopa E, Klinge P.Myodural bridges have been described in various species as connective tissue structures "bridging" small cranio-cervical muscles to the dura. Myodural bridges are thought to stabilize the dural sac during head and neck movements and promote cerebrospinal fluid motion; however, their role in neurological diseases has not yet been established. We report ultrasonographic visualization, necropsy, histopathologic and ultrastructural findings of myodural bridges in horses with hereditary equine regional dermal asthenia (HERDA), an equine model of Ehlers-Danlos syndromes. Five HERDA and 5 control hor...
Nykänen O, Sarin JK, Ketola JH, Leskinen H, Te Moller NCR, Tiitu V, Mancini IAD, Visser J, Brommer H, van Weeren PR, Malda J, Töyräs J, Nissi MJ.To investigate the potential of quantitative susceptibility mapping (QSM) and T2* relaxation time mapping to determine mechanical and structural properties of articular cartilage via univariate and multivariate analysis. Samples were obtained from a cartilage repair study, in which surgically induced full-thickness chondral defects in the stifle joints of seven Shetland ponies caused post-traumatic osteoarthritis (14 samples). Control samples were collected from non-operated joints of three animals (6 samples). Magnetic resonance imaging (MRI) was performed at 9.4 T, using a 3-D multi-echo gr...
Pusterla N, Chae JS, Kimsey RB, Berger Pusterla J, DeRock E, Dumler JS, Madigan JE.Most human granulocytic ehrlichiosis (HGE) studies carried out in horses use needle inoculation of infected leucocytes or cell cultures. This route of inoculation does not accurately reflect natural infection of the tick-borne agent. To investigate whether tick transmission influences the course of granulocytic ehrlichiosis in the horse model, experimental transmission through infected laboratory-reared Ixodes scapularis ticks was attempted into two healthy horses. One additional horse served as negative control and was exposed to uninfected ticks. Eleven days after exposure to nymphal or adul...
Bisgard GE, Forster HV, Byrnes B, Stanek K, Klein J, Manohar M.Ventilation, metabolism, arterial blood gases, and blood and cerebrospinal fluid (CSF) acid-base status were measured in exercise studies on seven ponies during mild, moderate, and near-maximal treadmill exercise. CSF and arterial blood were sampled via indwelling catheters. Generally measurements were made during the 3rd, 6th, and 9th minute of steady-state exercise, with CSF sampled only during the 9th minute. Alveolar ventilation (VA) and metabolic rate (VO2) increased proportionately during exercise below the anaerobic threshold, but above this threshold, VA increased at a faster rate than...
Campagne C, Julé S, Bernex F, Estrada M, Aubin-Houzelstein G, Panthier JJ, Egidy G.Melanocytic proliferations are common in horses but the diagnosis of malignancy is not always straightforward. To improve diagnosis and prognosis, markers of malignancy are needed. Receptor for activated C kinase 1 (RACK1) protein may be such a marker. RACK1 was originally found to characterize malignant melanocytic lesions in the Melanoblastoma-bearing Libechov minipig (MeLiM) and, later, in human patients. Our purpose was to investigate the value of RACK1 in the classification of cutaneous melanocytic proliferations in horses. Results: Using immunofluorescence, we report here that both MITF ...
Menarim BC, Gillis KH, Oliver A, Mason C, Ngo Y, Werre SR, Barrett SH, Luo X, Byron CR, Dahlgren LA.Osteoarthritis (OA) is characterized by macrophage-driven synovitis. Macrophages promote synovial health but become inflammatory when their regulatory functions are overwhelmed. Bone marrow mononuclear cells (BMNCs) are a rich source of macrophage progenitors used for treating chronic inflammation and produce essential molecules for cartilage metabolism. This study investigated the response to autologous BMNC injection in normal and inflamed joints. Synovitis was induced in both radiocarpal joints of 6 horses. After 8 h, 1 inflamed radiocarpal and 1 normal tarsocrural joint received BMNC injec...
Kim HY, Mott J, Zhi N, Tajima T, Rikihisa Y.Human granulocytic ehrlichiosis (HGE), a tick-borne zoonosis, is caused by an obligatory intragranulocytic bacterium, the HGE agent, a strain of Anaplasma phagocytophila. The equine model of HGE is considered valuable in understanding pathogenic and immune mechanisms of HGE. In the present study, cytokine mRNA expression by peripheral blood leukocytes (PBLs) in horses was examined during the course of infection by intravenous inoculation of A. phagocytophila or by allowing feeding by infected ticks. The p44 genes encoding the major outer membrane protein P44s of A. phagocytophila were detected...
Roth SP, Erbe I, Burk J.Reliable decellularization techniques applicable to tendon tissue play a critical role in the field of current tissue engineering. Particularly, an application as three-dimensional culture model for in vitro research and translational approaches to establish graft-based tendon repair as a routine clinical tool represent two main application fields for decellularized tendon scaffolds. Considering methodological issues of tendon decellularization, one of the major challenges lies in the preservation of the tendon-specific extracellular matrix (ECM) architecture to reflect natural tissue characte...
Hartl B, Hainisch EK, Shafti-Keramat S, Kirnbauer R, Corteggio A, Borzacchiello G, Tober R, Kainzbauer C, Pratscher B, Brandt S.Bovine papillomavirus types 1 and 2 (BPV-1 and BPV-2) are known to induce common equine skin tumours, termed sarcoids. Recently, it was demonstrated that vaccination with BPV-1 virus-like particles (VLPs) is safe and highly immunogenic in horses. To establish a BPV-1 challenge model for evaluation of the protective potential of BPV-1 VLPs, four foals were injected intradermally with infectious BPV-1 virions and with viral genome-based and control inocula, and monitored daily for tumour development. Blood was taken before inoculation and at weekly intervals. BPV-1-specific serum antibodies were...
González Vázquez AG, Blokpoel Ferreras LA, Bennett KE, Casey SM, Brama PA, O'Brien FJ.Joint repair remains a major challenge in orthopaedics. Recent progress in biomaterial design has led to the fabrication of a plethora of promising devices. Pre-clinical testing of any joint repair strategy typically requires the use of large animal models (e.g., sheep, goat, pig or horse). Despite the key role of such models in clinical translation, there is still a lack of consensus regarding optimal experimental design, making it difficult to draw conclusions on their efficacy. In this context, the authors performed a systematic literature review and a risk of bias assessment on large anima...
Mazzotti E, Teti G, Falconi M, Chiarini F, Barboni B, Mazzotti A, Muttini A.Osteoarthritis is a degenerative disease that strongly correlates with age and promotes the breakdown of joint cartilage and subchondral bone. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stromal cells (MSCs) isolated from adult tissues. It seems that MSCs derived from synovial joint tissues exhibit superior chondrogenic ability, but their unclear distribution and low frequency actually limit their clinical application. To date, the influence of aging on synovial joint derived MSCs' biological characteristics and differen...
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...
Mustonen AM, Lehmonen N, Oikari S, Capra J, Raekallio M, Mykkänen A, Paakkonen T, Rilla K, Niemelä T, Nieminen P.Osteoarthritis (OA) is a degenerative joint disease with inadequately understood pathogenesis leading to pain and functional limitations. Extracellular vesicles (EVs) released by synovial joint cells can induce both pro- and anti-OA effects. Hyaluronic acid (HA) lubricates the surfaces of articular cartilage and is one of the bioactive molecules transported by EVs. In humans, altered EV counts and composition can be observed in OA synovial fluid (SF), while EV research is in early stages in the horse-a well-recognized OA model. The aim was to characterize SF EVs and their HA cargo in 19 horses...
Ma TW, Li Y, Wang GY, Li XR, Jiang RL, Song XP, Zhang ZH, Bai H, Li X, Gao L.The study aimed to clarify the changes in the concentration of inflammatory mediators, proteases, and cartilage degradation biomarkers in the synovial fluid of joints in an equine osteoarthritis model. Methods: Osteoarthritis was induced in eight Mongolian horses by a sterile intra-articular injection of amphotericin B, which was injected into the left carpal joint in a dose of 2 mL (25 mg/mL). The control group comprised five horses which were injected with an equal dose of sterile physiological saline into the left carpal joint. Synovial fluid was obtained at baseline and every week after in...
Gilbertie JM, Schaer TP, Engiles JB, Seiler GS, Deddens BL, Schubert AG, Jacob ME, Stefanovski D, Ruthel G, Hickok NJ, Stowe DM, Frink A, Schnabel LV.The leading cause of treatment failure in Staphylococcus aureus infections is the development of biofilms. Biofilms are highly tolerant to conventional antibiotics which were developed against planktonic cells. Consequently, there is a lack of antibiofilm agents in the antibiotic development pipeline. To address this problem, we developed a platelet-rich plasma (PRP)-derived biologic, termed BIO-PLY (for the BIOactive fraction of Platelet-rich plasma LYsate) which has potent in vitro bactericidal activity against S. aureus synovial fluid free-floating biofilm aggregates. Additional in vitro st...
Clauss M, Loehlein W, Kienzle E, Wiesner H.In order to test the suitability of the horse as a nutritional model for elephants, digestibility studies were performed with six captive Asian elephants on six different dietary regimes, using the double marker method with acid detergent lignin as an internal and chromium oxide as an external digestibility marker. Elephants resembled horses in the way dietary supplements and dietary crude fibre content influenced digestibility, in calcium absorption parameters and in faecal volatile fatty acid composition. However, the absolute digestibility coefficients achieved for all nutrients are distinc...
Litzke LE, Wagner E, Baumgaertner W, Hetzel U, Josimović-Alasević O, Libera J.Damaged adult articular cartilage has very limited capacity to heal. Autologous chondrocyte transplantation (ACT) has been used clinically and studied in experimental animals in an attempt to provide biologically based cartilage regeneration. This study evaluated cartilage repair following ACT in a large animal model over a period of 2 years. Articular cartilage defects (10 mm in diameter, full-thickness) were created in the minor load-bearing area on the lateral talus of tibiotarsal joints of eight adult horses. In each animal, the right joint was repaired using autologous chondrocytes inject...
Cullier A, Cassé F, Manivong S, Contentin R, Legendre F, Garcia Ac A, Sirois P, Roullin G, Banquy X, Moldovan F, Bertoni L, Audigié F, Galéra P....Osteoarthritis (OA) is a degenerative and heterogeneous disease that affects all types of joint structures. Current clinical treatments are only symptomatic and do not manage the degenerative process in animals or humans. One of the new orthobiological treatment strategies being developed to treat OA is the use of drug delivery systems (DDS) to release bioactive molecules over a long period of time directly into the joint to limit inflammation, control pain, and reduce cartilage degradation. Two vasoactive peptides, endothelin-1 and bradykinin, play important roles in OA pathogenesis. In this ...
Ketchum CC, Larsen CD, McNeil A, Meyer-Ficca ML, Meyer RG.Chromatin remodeling during spermatogenesis culminates in the exchange of nucleosomes for transition proteins and protamines as an important part of spermatid development to give rise to healthy sperm. Comparative immunofluorescence analyses of equine and murine testis histological sections were used to characterize nucleoprotein exchange in the stallion. Histone H4 hyperacetylation is considered a key event of histone removal during the nucleoprotein transition to a protamine-based sperm chromatin structure. In the stallion, but not the mouse, H4 was already highly acetylated in lysine residu...
Seeto WJ, Tian Y, Winter RL, Caldwell FJ, Wooldridge AA, Lipke EA.A common challenge in cell therapy is the inability to routinely maintain survival and localization of injected therapeutic cells. Delivering cells by direct injection increases the flexibility of clinical applications, but may cause low cell viability and retention rates due to the high shear forces in the needle and mechanical wash out. In this study, we encapsulated endothelial colony forming cells (ECFCs) in poly(ethylene glycol)-fibrinogen (PF) hydrogel microspheres using a custom-built microfluidic device; this system supports rapid encapsulation of high cell concentrations (10 million c...
Ginther OJ, Beg MA, Gastal EL, Gastal MO, Baerwald AR, Pierson RA.Changes in systemic concentrations of FSH, LH, oestradiol and progesterone during the ovulatory follicular wave were compared between 30 mares and 30 women. Based on a previous study, the emergence of the future ovulatory follicle was defined as occurring at 13.0 mm in mares and 6.0 mm in women, and deviation in diameter between the two largest follicles was expected to begin at 22.7 mm in mares and 10.3 mm in women. Mean FSH concentrations were high in mares during the luteal phase, resulting from statistically identified FSH surges occurring in individuals on different days and in different ...
Saljic A, Friederike Fenner M, Winters J, Flethøj M, Eggert Eggertsen C, Carstensen H, Dalgas Nissen S, Melis Hesselkilde E, van Hunnik A....Fibroblasts maintain the extracellular matrix homeostasis and may couple to cardiomyocytes through gap junctions and thereby increase the susceptibility to slow conduction and cardiac arrhythmias, such as atrial fibrillation (AF). In this study, we used an equine model of persistent AF to characterize structural changes and the role of fibroblasts in the development of an arrhythmogenic substrate for AF. Methods: Eleven horses were subjected to atrial tachypacing until self-sustained AF developed and were kept in AF for six weeks. Horses in sinus rhythm (SR) served as control. In terminal open...
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...
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...
Klier J, Geis S, Steuer J, Geh K, Reese S, Fuchs S, Mueller RS, Winter G, Gehlen H.New therapeutic strategies to modulate the immune response of human and equine allergic asthma are still under extensive investigation. Immunomodulating agents stimulating T-regulatory cells offer new treatment options beyond conventional symptomatic treatment or specific immunotherapy for human and equine allergic airway diseases, with the goal of a homoeostatic T-helper cell balance. The aim of this study was to evaluate the effects of a nebulized gelatin nanoparticle-CpG formulation (CpG-GNP) with and without specific allergens for the treatment of spontaneous allergic equine asthma as a mo...
Carnevale EM, Catandi GD, Fresa K.Numerous similarities in reproductive aging have been documented between the mare and woman. Aging is associated with a decline in fertility. In mares and women, oocyte transfer procedures were initially used to establish that oocyte donor age is associated with oocyte quality. Age-associated differences in oocytes include altered morphology, gene expression, and developmental potential. Reactive oxygen species and mitochondrial dysfunction are thought to be important contributors to loss of oocyte quality. In the woman, aneuploidy is a primary consideration with maternal aging. Although misal...
Baumann C, Daly CM, McDonnell SM, Viveiros MM, De La Fuente R.Pairing of the sex chromosomes during mammalian meiosis is characterized by the formation of a unique heterochromatin structure at the XY body. The mechanisms underlying the formation of this nuclear domain are reportedly highly conserved from marsupials to mammals. In this study, we demonstrate that in contrast to all eutherian species studied to date, partial synapsis of the heterologous sex chromosomes during pachytene stage in the horse is not associated with the formation of a typical macrochromatin domain at the XY body. While phosphorylated histone H2AX (γH2AX) and macroH2A1.2 are pres...
Venugopal CS, Eades S, Holmes EP, Beadle RE.One of the causes of equine laminitis is hyperinsulinaemia, which may be associated with endothelial dysfunction and insulin resistance of vessels. Objective: Insulin resistance can be induced in palmar digital vessels by continued exposure to insulin in vitro. The objective was to evaluate this in vitro model for future studies. Methods: Palmar digital vessel segments were collected immediately after euthanasia from horses with normal insulin/glucose blood values. Four arterial and 4 venous rings (3 mm wide) were prepared and each ring mounted in a tissue bath, containing Tyrode's solution at...
Johnson PJ, Janvier V, Luh WM, FitzMaurice M, Southard T, Barry EF.There is growing interest in the horse for behavioral, neuroanatomic and neuroscientific research due to its large and complex brain, cognitive abilities and long lifespan making it neurologically interesting and a potential large animal model for several neuropsychological diseases. Magnetic resonance imaging (MRI) is a powerful neuroscientific research tool that can be performed , with adapted equine facilities, or in the research setting. The brain atlas is a fundamental resource for neuroimaging research, and have been created for a multitude animal models, however, none currently exist f...
Ealy AD, Eroh ML, Sharp DC.The equine embryo must signal its presence to the uterus for pregnancy to continue to term. Mobility of the conceptus throughout the uterus is crucial for its survival, and this action presumably permits the conceptus to transmit its antiluteolytic signal to the endometrium. Studies were completed to establish whether this unidentified antiluteolytic signal targets prostaglandin G/H synthase 2 (PGHS2), a rate limiting enzyme in converting arachidonic acid to prostaglandins (PGs). In the first study, quantitative RT-PCR was used to determine the relative abundance of PGHS2 mRNA in endometrium d...
Svala E, Löfgren M, Sihlbom C, Rüetschi U, Lindahl A, Ekman S, Skiöldebrand E.The molecular aspects of inflammation were investigated in equine articular cartilage explants using quantitative proteomics. Articular cartilage explants were stimulated with interleukin (IL)-1β in vitro for 25 days, and proteins released into cell culture media were chemically labeled with isobaric mass tags and analyzed by liquid chromatography-tandem mass spectrometry. A total of 127 proteins were identified and quantified in media from explants. IL-1β-stimulation resulted in an abundance of proteins related to inflammation, including matrix metalloproteinases, acute phase proteins, comp...
Salonius E, Rieppo L, Nissi MJ, Pulkkinen HJ, Brommer H, Brünott A, Silvast TS, Van Weeren PR, Muhonen V, Brama PAJ, Kiviranta I.The horse joint, due to its similarity with the human joint, is the ultimate model for translational articular cartilage repair studies. This study was designed to determine the critical size of cartilage defects in the equine carpus and serve as a benchmark for the evaluation of new cartilage treatment options. Circular full-thickness cartilage defects with a diameter of 2, 4, and 8 mm were created in the left middle carpal joint and similar osteochondral (3.5 mm in depth) defects in the right middle carpal joint of 5 horses. Spontaneously formed repair tissue was examined macroscopically, ...
