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.
Vachkova E, Arnhold S, Petrova V, Heimann M, Koynarski T, Simeonova G, Piperkov P.The impact of donor age on Adipose-derived mesenchymal stem cell (ASC) functionality and safety remains insufficiently characterized, particularly in equine models. This study investigates the influence of age on ASCs proliferation dynamics and the expression of tumorigenic and apoptosis-related markers. Equine ASCs were isolated from juvenile (<5 years), middle-aged (5-15 years), and geriatric (>15 years) horses and assayed across multiple passages. The relative mRNA expressions of pluripotency (Oct4), tumorigenic (CA9), and apoptosis-related (Bax and Bcl 2) markers were evaluated. The Gomper...
Koch DW.Our understanding of tendon homeostasis and repair following injury has made great strides through basic science, clinical veterinary medicine, and preclinical translational research. We have now gleaned a greater understanding of the cellular and matrix dynamics that are being orchestrated within the tendon, which provide therapeutic opportunities. This article will focus on how utilizing the horse and equine tissues have advanced our understanding of tendinopathy and the cellular and matrix dynamics at play while also identifying continued gaps in our knowledge where the horse as a veterinar...
Fakhar-I-Adil M, Angel-Velez D, Araftpoor E, Amin QA, Hedia M, Bühler M, Gevaert K, Menten B, Van Soom A, Chuva de Sousa Lopes SM, Stoop D, De Roo C....In vitro maturation (IVM) of oocytes retrieved from ovum pick-up (OPU) or ovarian tissue (OT) is a standard approach for patients with specific conditions where prior hormonal stimulation is contraindicated. However, the developmental competence of oocytes matured in vitro is still inferior to that of oocytes matured in vivo. Capacitation IVM (CAPA-IVM) includes an extra step of pre-maturation culture (PMC) with c-type natriuretic peptide (CNP) as a meiotic arrestor to better synchronize cytoplasmic and nuclear maturity in oocytes by allowing the cytoplasm additional time to acquire essential ...
Santiviparat S, Suthithanakom S, Bhanpattanakul S, Srisuwattanasagul S, Melde K, Stout TAE, Tharasanit T.Advances in endometrial tissue engineering have enabled the combination of modified scaffolding materials with modern cell culture technologies. Genipin and three-dimensional (3D) printing have advanced cell-tissue engineering by enabling the precise layering of cell-containing matrices while ensuring low cytotoxicity. This study aimed to advance equine endometrial tissue engineering by designing customized collagen scaffolds using 3D printing technology, while optimizing the genipin concentration to avoid toxicity. Genipin was tested at concentrations of 4, 2, 1, 0.5, 0.25, 0.125, and 0 mM on...
Lab on a chipMay 28, 2025
Volume 25, Issue 11 2795-2796 doi: 10.1039/d5lc90048d
Heidenberger J, Reihs EI, Strauss J, Frauenlob M, Gültekin S, Gerner I, Toegel S, Ertl P, Windhager R, Jenner F, Rothbauer M.Correction for 'The effect of cyclic fluid perfusion on the proinflammatory tissue environment in osteoarthritis using equine joint-on-a-chip models' by Johannes Heidenberger et al., Lab Chip, 2025, 25, 2256-2269, https://doi.org/10.1039/d4lc01078g.
Euppayo T, Siengdee P, Limlenglert P, Nganvongpanit K, Watanabe G, Kasashima Y, Arai K.The self-renewal capacity of chondrocytes in osteoarthritis (OA) joints is limited, and mesenchymal stem cells (MSCs) are crucial in disease treatment. This study established an OA model from equine bone marrow-derived mesenchymal stem cells (eBMSCs). The eBMSCs were cultured and differentiated into chondrocytes to generate cartilage pellets, which were induced for 7 d with inflammatory cytokines, interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) to mimic OA conditions. Treated culture medium was collected to estimate enzyme activity (MMP-2, MMP-3, and MMP-9) using zymograph...
Kadic LIM, Liu CC, Riggs LM.The aim of this study was to compare the monotonic tensile strength and fatigue strength of a stainless steel cable (SSC) compared to a human non-metallic polymer cable (NMPC) in an metacarpophalangeal joint arthrodesis model lacking a dorsal plate application.An experimental biomechanical equine cadaver limb study. Ten metacarpophalangeal joints were collected from five adult Thoroughbred horses, euthanatized for reasons unrelated to orthopaedic disease. Each pair of metacarpophalangeal joints was randomly instrumented with either a 1.7-mm SSC or a NMPC. Each construct was tested in cyclic ...
Avison A, Physick-Sheard PW, Pyle WG.This paper reviews the myocardial substrate of horses relative to that of humans and discusses the utility of performance horses as a model of exercise-associated cardiac arrhythmias and sudden cardiac death in athletes. The coronary circulation is similar between the species while coronary artery anomalies and myocardial bridging appear to only be associated with athletic mortality in human athletes and not in performance horses. There are subtle differences in the histology of the sinus and atrioventricular nodes, of unknown clinical significance, while the His bundle is more highly innervat...
Heidenberger J, Reihs EI, Strauss J, Frauenlob M, Gültekin S, Gerner I, Tögel S, Ertl P, Windhager R, Jenner F, Rothbauer M.Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage degradation, chronic inflammation, and progressive joint dysfunction. Despite rising incidences driven by ageing and increasing obesity, potent treatments remain elusive, exacerbating the socioeconomic burden. OA pathogenesis involves an imbalance in extracellular matrix (ECM) turnover, mediated by inflammatory cytokines and matrix-degrading enzymes, leading to oxidative stress, chondrocyte apoptosis, and ECM degradation. Additionally, synovial inflammation (synovitis) plays a critical role in disease pro...
O'Kennedy MM, Reedy SE, Abolnik C, Khan A, Smith T, du Preez I, Olajide E, Daly J, Cullinane A, Chambers TM.Equine influenza (EI) is a highly contagious acute respiratory disease of wild and domesticated horses, donkeys, mules, and other Equidae. EI is caused by the Equine Influenza virus (EIV), is endemic in many countries and outbreaks still have a severe impact on the equine industry globally. Conventional EI vaccines are widely used, but a need exists for a platform that facilitates prompt manufacturing of a highly immunogenic, antigenically matched, updated vaccine product. Here we developed a plant-produced bivalent EI virus-like particle (VLP) vaccine candidate which lacks the viral genome an...
Beaumont RE, Smith EJ, David C, Paterson YZ, Faull E, Guest DJ.Tendon injuries are a common problem in humans and horses. There is a high re-injury rate in both species due to the poor regeneration of adult tendon and the resulting formation of scar tissue. In contrast, fetal tendon injuries undergo scarless regeneration, but the mechanisms which underpin this are poorly defined. It is also unclear if tendon cells derived from embryonic stem cells (ESCs) would aid tendon regeneration. In this study we determined the responses of adult, fetal and ESC-derived equine tenocytes to a range of cytokines, chemokines and growth factors that are upregulated follow...
Breen LJ, Stack JD, Gillen AM, Baldwin CM.(1) To evaluate the feasibility of needle tenoscopy of the digital flexor tendon sheath (DFTS) using basisesamoid (BS) and proximolateral (PL) approaches in a standing equine cadaver model. (2) To report visualization of intrathecal DFTS anatomy via both approaches. (3) To determine the efficacy of needle scope-guided palmar/plantar annular ligament (PAL) desmotomy. (4) To report any iatrogenic damage associated with the procedure. Methods: Ex vivo experimental. Methods: Ten equine cadaver limbs. Methods: Limbs were placed in a Kimzey leg-saver splint and needle tenoscopy was performed using t...
Scheike AS, Plomp S, Fugazzola MC, Meurot C, Berenbaum F, van Weeren PR, Tryfonidou MA, von Hegedus JH.This study investigates the anti-inflammatory properties of liraglutide, a glucagon-like peptide 1 receptor agonists, in equine in vitro models and in an in vivo acute synovitis model in Shetland ponies. The anti-inflammatory effect of liraglutide was assessed by measuring concentrations of inflammatory biomarker C-C Motif Chemokine Ligand 2 (CCL2) in culture media of equine whole blood, peripheral blood mononuclear cells (PBMCs), chondrocytes, and synoviocytes, with or without lipopolysaccharide (LPS) or interleukin-1β. In the in vivo experiment, acute synovitis was bilaterally induced with ...
Campebell RC, Oliveira AB, Fagundes JLA, Fortes BNA, Veado HC, Macedo IL, Dallago BSL, Barud HS, Adorno J, Salvador PAV, Santos PS, Castro MB.This study evaluates the wound-healing process in horses following the application of two treatment modalities: bacterial cellulose hydrogel with alginate (BCAW) and frog skin (FSW) dressings on experimentally induced skin wounds. Throughout the experiment, no clinical abnormalities were noted in the horses, although initial wound assessments indicated edema and sensitivity. Local hemorrhage was observed in some cases on Day 0, with granulation tissue formation evident by Day 14. Epithelialization began around Day 14 but did not reach complete healing in any group by Day 28. The analysis showe...
Harbowy RM, Nielsen BD, Colbath AC, Robison CI, Buskirk DD, Logan AA.Though circular exercise is commonly used in equestrian disciplines, it may be at the detriment of horses' musculoskeletal system. To investigate the effects of circular exercise on bone and joint health, 42 lambs were randomly assigned to a non-exercised control, straight-line, small circle, or large circle exercise regime at a slow (1.3 m/s) or fast (2.0 m/s) speed for 12 wk. Blood samples were taken biweekly. Animals were humanely euthanized upon study completion, and the fused third and fourth metacarpals were collected for biomechanical testing and bone density analysis. Fast groups were ...
Luedke LK, Seabaugh KA, Cooper BG, Snyder BD, Wimmer MA, McIlwraith CW, Barrett MF, Kawcak CE, Grinstaff MW, Goodrich LR.Post-traumatic osteoarthritis (PTOA) is a common cause of lameness in the horse. There is no cure, therefore treatments are aimed at reducing pain and improving the joint environment by modifying inflammatory pathways or by viscosupplementation. Here, we report the safety and efficacy of the biolubricant (poly(2-methacryloyloxyethyl phosphorylcholine; pMPC) to mitigate the physical, gross, histological, and biochemical effects of arthritis. We created an osteochondral fragment in the middle carpal joint of one limb in 16 horses to induce PTOA; the contralateral limb served as a sham-operated j...
Hickman E, Carberry V, Carberry C, Cooper B, Mordant AL, Mills A, Sokolsky M, Herring LE, Alexis NE, Rebuli ME, Jaspers I, Sheats K, Rager JE.Growing evidence supports the importance of extracellular vesicle (EV) as mediators of communication in pathological processes, including those underlying respiratory disease. However, establishing methods for isolating and characterizing EVs remains challenging, particularly for respiratory samples. This study set out to address this challenge by comparing different EV isolation methods and evaluating their impacts on EV yield, markers of purity, and proteomic signatures, utilizing equine/horse bronchoalveolar lavage samples. Horses can serve as effective translational animal models for respi...
Sauter PK, Steblaj B, Kästner SBR, Söbbeler FJ, Reiners JK, Kutter APN, Bautitsta AJG, Neudeck S.Microcirculation is the essential link between macrocirculation and cellular metabolism. Objective: To test our hypotheses that microcirculation variables will show a heterogeneous flow pattern during experimental endotoxaemia, and that fluid therapy and noradrenaline (NA) infusion will normalise altered microcirculation variables. Methods: In vivo experiments. Methods: Six healthy adult horses were anaesthetised with dexmedetomidine, ketamine, and diazepam and were mechanically ventilated under isoflurane anaesthesia. Endotoxaemia was induced with 30 ng kg Escherichia coli lipopolysacchar...
Myćka G, Ropka-Molik K, Cywińska A, Stefaniuk-Szmukier M.Among numerous genes that have been a focus of equine genetic research, the (Klotho) and (Alpha-actinin-3) genes stand out due to their significant roles in muscle function and overall health, as well as performance ability. Previous studies on Arabian horses and other mammalians have shown that both and occur in different isoforms that seem to have different roles in metabolism. The main purpose of this present study was to describe different isoforms (, , , , , ) expression levels affected by the endurance effort in Arabian horses. Methods: Blood samples were taken from a group of = 10 ...
Itoh K, Kikumura N, Maeda T, Hirata S, Ringhofer M.Despite the long history of the horse-human bond, our understanding of the brain and mind of horses remains limited due to the lack of methods to investigate their brain functions. This study introduces a novel methodology for completely non-invasive, multi-channel recording of electroencephalography (EEG) and evoked potentials in awake horses to examine equine auditory cortical processing. The new approach utilizes specially designed brush-shaped active electrodes that facilitate stable signal acquisition through the hair coat by penetrating electrode pins and integrated pre-amplifiers. A 12-...
Resende AM, Miranda BA, Silva LB, Oliveira AB, Castro MB, Macêdo IL, Dallago BSL, Barud HS, Borges MAC, Ribeiro CA, Dias DS, Campebell RC.Background/Objectives: Skin injuries are common in the equine clinical practice, requiring effective treatment to support natural healing. Bacuri butter is gaining attention for its potential in wound healing and its anti-inflammatory, antimicrobial, and antioxidant properties. Natural polymers such as onion (Allium cepa) bioplastics have been investigated for their potential as occlusive dressings and for tissue regeneration. Methods: This study evaluated the healing process of experimentally induced skin wounds on horses treated with bacuri butter, washed onion film, and unwashed onion film....
Mersich I, Bishop RC, Diaz Yucupicio S, Nobrega AD, Austin SM, Barger AM, Fick ME, Wilkins PA.Coagulopathy is common in equine critical illness, with its early recognition being crucial for patient management and prognosis. In vitro viscoelastic (VE) hypercoagulability with decreased RCM/PCV has been demonstrated in dogs but not horses. Our objective was to evaluate the effects of acepromazine-induced (0.1 mg/kg IV) decreased RCM on VE and plasma coagulation parameters using a prospective interventional study of eight adult horses. Complete blood count (CBC), fibrinogen, prothrombin time (PT), partial thromboplastin time (PTT), packed cell volume (PCV), total solids (TS), and VCM Vetâ„...
Stewart AS, Kopper JJ, McKinney-Aguirre C, Veerasamy B, Sahoo DK, Freund JM, Gonzalez LM.Gastrointestinal disease is a leading cause of death in mature horses. A lack of in vitro modeling has impeded the development of novel therapeutics. The objectives of this study were to develop and further characterize a small intestinal monolayer cell culture derived from equine jejunum including establishing normal measurements of intestinal permeability and restitution. Three-dimensional enteroids, derived from postmortem sampling of equine jejunum, were utilized to develop confluent epithelial monolayers. The presence of differentiated intestinal epithelial cell types and tight junctions ...
Nishimura F, Fukushi N, Sakai H, Fukushi H.Equine herpesvirus type 1 (EHV-1) causes abortion, respiratory infection, and neurological diseases (equine herpesvirus myeloencephalopathy) in horses. A single nucleotide polymorphism (SNP) associated with a single amino acid in the DNA polymerase gene (ORF30, in which D752 is neuropathogenic and N752 is non-neuropathogenic) of EHV-1 has been associated with neuropathogenicity in horses. We constructed an EHV-1 Ab4p ORF30 N752 mutant and a repair virus to examine the effect of a D752N mutation on the neuropathogenicity of the virus in Syrian hamsters. The N752 mutation did not affect viral gr...
Fahey MJ, Harman RM, Thomas MA, Pugliese BR, Peters-Kennedy J, Delco ML, Van de Walle GR.We aimed to study the antimicrobial and pro-healing potential of equine mesenchymal stromal cell secreted products (i.e. secretome), collected as conditioned media (mesenchymal stromal cell-conditioned media, MSC CM), in a novel in vivo model of methicillin-resistant Staphylococcus aureus (MRSA)-inoculated equine thorax wounds. Methods: Prospective in vivo study. Methods: Two Thoroughbred geldings. Methods: Six full-thickness cutaneous wounds were created bilaterally on the dorsal thorax of two horses (n = 12 wounds/horse). Wounds on the left thoraces were inoculated with MRSA on day 0. Al...
Lessiak U, Melchert M, Walter I, Kummer S, Nell B, Tschulenk W, Pratscher B.Angiogenesis plays a crucial role in various physiological and pathological conditions. However, research in equine angiogenesis is relative limited, necessitating the development of suitable models. To effectively analyze angiogenesis in-vitro, it is essential to target the specific cells responsible for this process, namely endothelial cells. Human umbilical vein endothelial cells (HUVECs) are one of the most used models for studying angiogenesis in humans. Serving as an equivalent to HUVECs, we present a comprehensive isolation protocol for equine umbilical vein endothelial cells (EqUVECs...
Serteyn D, Storms N, Mouithys-Mickalad A, Sandersen C, Niesten A, Duysens J, Graide H, Ceusters J, Franck T.Laminitis in horses is a crippling condition marked by the deterioration of the dermal-epidermal interface, leading to intense lameness and discomfort, often necessitating euthanasia. This study aimed to establish an in vitro model of laminitis using a continuous keratinocyte cell line exposed to anoxia-reoxygenation and an activated neutrophil supernatant. A significant decrease in the keratinocytes' metabolism was noted during the reoxygenation period, indicative of cellular stress. Adding muscle-derived mesenchymal stem/stromal cells during the reoxygenation demonstrated a protective effect...
McCarrel TM, Cole C, Maxwell LK, Roe HA, Morton AJ.To determine (1) the dose of liposomal bupivacaine (LB) to eliminate grade 2 of 5 lameness, the (2) duration of analgesia of LB versus bupivacaine hydrochloride (BH), and (3) LB pharmacokinetics versus BH. Methods: A reversible lameness model was validated in conditioned Thoroughbred horses (n = 12), aged 3 to 10 years. A dose-response trial compared subjective and objective lameness following abaxial sesamoid block with 25 mg BH/nerve or 30, 60, or 133 mg LB/nerve (n = 3/group). The LB dose that eliminated lameness and reduced lameness for the longest was used for blinded, randomized, crossov...
Woodrow JS, Palmisano M, Kulp J, Hopster K.Complications from general anesthesia, including pneumonia and decreased wound healing, are influenced by changes in immune cell function secondary to sedatives and anesthetics. It was hypothesized that immune cell function would be depressed in the early postanesthetic period. The objective was to investigate airway immune cell function before and after a general anesthetic episode in an equine in vivo model using ex vivo cell stimulations with lipopolysaccharide (LPS) for assessment of immune function. Methods: Prospective experimental study. Methods: Six healthy, adult, institution-owned ...
Lawson JM, Salem SE, Miller D, Kahler A, van den Boer WJ, Shilton CA, Sever T, Mouncey RR, Ward J, Hampshire DJ, Foote AK, Bryan JS, Juras R, Pynn OD....Chromosomal abnormalities are a common cause of human miscarriage but rarely reported in any other species. As a result, there are currently inadequate animal models available to study this condition. Horses present one potential model since mares receive intense gynecological care. This allowed us to investigate the prevalence of chromosomal copy number aberrations in 256 products of conception (POC) in a naturally occurring model of pregnancy loss (PL). Triploidy (three haploid sets of chromosomes) was the most common aberration, found in 42% of POCs following PL over the embryonic period. O...
Ramsay JD, Evanoff R, Wilkinson TE, Divers TJ, Knowles DP, Mealey RH.Equine hepacivirus (EHCV; nonprimate hepacivirus) is a hepatotropic member of the Flaviviridae family that infects horses. Although EHCV is the closest known relative to hepatitis C virus (HCV), its complete replication kinetics in vivo have not been described, and direct evidence that it causes hepatitis has been lacking. In this study, we detected EHCV in 2 horses that developed post-transfusion hepatitis. Plasma and serum from these horses were used to experimentally transmit EHCV to 4 young adult Arabian horses, two 1-month-old foals (1 Arabian and 1 Arabian-pony cross), and 2 foals (1 Ara...
Arnhold SJ, Goletz I, Klein H, Stumpf G, Beluche LA, Rohde C, Addicks K, Litzke LF.To isolate and characterize bone marrow-derived equine mesenchymal stem cells (MSCs) for possible future therapeutic applications in horses. Methods: Equine MSCs were isolated from bone marrow aspirates obtained from the sternum of 30 donor horses. Methods: Cells were cultured in medium (alpha-minimum essential medium) with a fetal calf serum content of 20%. Equine MSC features were analyzed to determine selfrenewing and differentiation capacity. For potential therapeutic applications, the migratory potential of equine MSCs was determined. An adenoviral vector was used to determine the transdu...
Bussche L, Van de Walle GR.Mesenchymal stromal cells (MSCs) have received much attention as a potential treatment of ischemic diseases, including ischemic tissue injury and cardiac failure. The beneficial effects of MSCs are thought to be mediated by their ability to provide proangiogenic factors, creating a favorable microenvironment that results in neovascularization and tissue regeneration. To study this in more detail and to explore the potential of the horse as a valuable translational model, the objectives of the present study were to examine the presence of angiogenic stimulating factors in the conditioned medium...
Torricelli P, Fini M, Filardo G, Tschon M, Pischedda M, Pacorini A, Kon E, Giardino R.Tissue repair in musculoskeletal injuries is often a slow and sometimes incomplete process. Regenerative medicine based on the use of growth factors (GFs) and cell therapy is aimed at improving the quality and speed of tendon and ligament healing. The aim of this study was to evaluate the potential for the administration of a combination of autologous platelet-rich plasma (PRP) and freshly isolated bone marrow mononucleated cells (BMMNCs) in 13 competition horses affected by overuse musculoskeletal injuries (suspensory ligament desmopathy and superficial flexor tendinopathy) and refractory to ...
Watts AE, Yeager AE, Kopyov OV, Nixon AJ.Tendon injury is a common problem in athletes, with poor tissue regeneration and a high rate of re-injury. Stem cell therapy is an attractive treatment modality as it may induce tissue regeneration rather than tissue repair. Currently, there are no reports on the use of pluripotent cells in a large animal tendon model in vivo. We report the use of intra-lesional injection of male, fetal derived embryonic-like stem cells (fdESC) that express Oct-4, Nanog, SSEA4, Tra 1-60, Tra 1-81 and telomerase. Methods: Tendon injury was induced using a collagenase gel-physical defect model in the mid-metacar...
Seino KK, Long MT, Gibbs EP, Bowen RA, Beachboard SE, Humphrey PP, Dixon MA, Bourgeois MA.We used a severe challenge model that produces clinical West Nile virus (WNV) disease to test the efficacy of three commercially available equine WNV vaccines in horses. Twenty-four healthy, WNV-seronegative horses of varying ages and genders were placed, in random and blind manner, into three trial groups consisting of eight horses each; two horses in each group received (i) an inactivated WNV vaccine (K-WN), (ii) a modified-live vaccine (CP-WN) containing the WNV prM and E proteins expressed by a canarypox vector, (iii) a live-chimera vaccine (WN-FV) containing WNV prM and E proteins express...
Leclere M, Lavoie-Lamoureux A, Joubert P, Relave F, Setlakwe EL, Beauchamp G, Couture C, Martin JG, Lavoie JP.Recent studies suggest that airway smooth muscle remodeling is an early event in the course of asthma. Little is known of the effects of long-term antigen avoidance and inhaled corticosteroids on chronically established airway remodeling. We sought to measure the effects of inhaled corticosteroids and antigen avoidance on airway remodeling in the peripheral airways of horses with heaves, a naturally occurring asthma-like disease. Heaves-affected adult horses with ongoing airway inflammation and bronchoconstriction were treated with fluticasone propionate (with and without concurrent antigen av...
Hidaka C, Goodrich LR, Chen CT, Warren RF, Crystal RG, Nixon AJ.Cartilage has a limited capacity to heal. Although chondrocyte transplantation is a useful therapeutic strategy, the repair process can be lengthy. Previously we have shown that over expression of bone morphogenetic protein-7 (BMP-7) in chondrocytes by adenovirus-mediated gene transfer leads to increased matrix synthesis and cartilage-like tissue formation in vitro. In this context we hypothesized that implantation of genetically modified chondrocytes expressing BMP-7 would accelerate the formation of hyaline-like repair tissue in an equine model of cartilage defect repair. Methods: Chondrocyt...
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...
Dakin SG, Werling D, Hibbert A, Abayasekara DR, Young NJ, Smith RK, Dudhia J.Macrophages (Mφ) orchestrate inflammatory and reparatory processes in injured connective tissues but their role during different phases of tendon healing is not known. We investigated the contribution of different Mφ subsets in an equine model of naturally occurring tendon injury. Post mortem tissues were harvested from normal (uninjured), sub-acute (3-6 weeks post injury) and chronically injured (>3 months post injury) superficial digital flexor tendons. To determine if inflammation was present in injured tendons, Mφ sub-populations were quantified based on surface antigen expression of...
Rivas F, Zahid OK, Reesink HL, Peal BT, Nixon AJ, DeAngelis PL, Skardal A, Rahbar E, Hall AR.Hyaluronan (or hyaluronic acid, HA) is a ubiquitous molecule that plays critical roles in numerous physiological functions in vivo, including tissue hydration, inflammation, and joint lubrication. Both the abundance and size distribution of HA in biological fluids are recognized as robust indicators of various pathologies and disease progressions. However, such analyses remain challenging because conventional methods are not sufficiently sensitive, have limited dynamic range, and/or are only semi-quantitative. Here we demonstrate label-free detection and molecular weight discrimination of HA w...
Marx C, Gardner S, Harman RM, Van de Walle GR.Mesenchymal stromal cells (MSCs) from various species, such as humans, mice, and horses, were recently found to effectively inhibit the growth of various bacteria associated with chronic infections, such as nonhealing cutaneous wounds, via secretion of antimicrobial peptides. These MSC antimicrobial properties have primarily been studied in the context of the planktonic phenotype, and thus, information on the effects on bacteria in biofilms is largely lacking. The objectives of this study were to evaluate the in vitro efficacy of the MSC secretome against various biofilm-forming wound pathogen...
Ambruosi B, Uranio MF, Sardanelli AM, Pocar P, Martino NA, Paternoster MS, Amati F, Dell'Aquila ME.Phthalates are ubiquitous environmental contaminants because of their use in plastics and other common consumer products. Di-(2-ethylhexyl) phthalate (DEHP) is the most abundant phthalate and it impairs fertility by acting as an endocrine disruptor. The aim of the present study was to analyze the effects of in vitro acute exposure to DEHP on oocyte maturation, energy and oxidative status in the horse, a large animal model. Cumulus cell (CC) apoptosis and oxidative status were also investigated. Cumulus-oocyte complexes from the ovaries of slaughtered mares were cultured in vitro in presence of...
Golafshan N, Vorndran E, Zaharievski S, Brommer H, Kadumudi FB, Dolatshahi-Pirouz A, Gbureck U, van Weeren R, Castilho M, Malda J.One of the important challenges in bone tissue engineering is the development of biodegradable bone substitutes with appropriate mechanical and biological properties for the treatment of larger defects and those with complex shapes. Recently, magnesium phosphate (MgP) doped with biologically active ions like strontium (Sr) have shown to significantly enhance bone formation when compared with the standard calcium phosphate-based ceramics. However, such materials can hardly be shaped into large and complex geometries and more importantly lack the adequate mechanical properties for the treatment ...
Kirkpatrick JF, Lyda RO, Frank KM.Wildlife, free-ranging and captive, poses and causes serious population problems not unlike those encountered with human overpopulation. Traditional lethal control programs, however, are not always legal, wise, safe, or publicly acceptable; thus, alternative approaches are necessary. Immunocontraception of free-ranging wildlife has reached the management level, with success across a large variety of species. Thus far, the immunocontraceptive research and management applications emphasis have been centered on porcine zona pellucida and gonadotropin-releasing hormone vaccines. Contraceptive succ...
Watts AE, Millar NL, Platt J, Kitson SM, Akbar M, Rech R, Griffin J, Pool R, Hughes T, McInnes IB, Gilchrist DS.Tendon injuries (tendinopathies) are common in human and equine athletes and characterized by dysregulated collagen matrix, resulting in tendon damage. We have previously demonstrated a functional role for microRNA29a (miR29a) as a post-transcriptional regulator of collagen 3 expression in murine and human tendon injury. Given the translational potential, we designed a randomized, blinded trial to evaluate the potential of a miR29a replacement therapy as a therapeutic option to treat tendinopathy in an equine model that closely mimics human disease. Tendon injury was induced in the superficial...
Brossi PM, Moreira JJ, Machado TS, Baccarin RY.This systematic review aimed to present and critically appraise the available information on the efficacy of platelet rich plasma (PRP) in equine and human orthopedic therapeutics and to verify the influence of study design and methodology on the assumption of PRP's efficacy. We searched Medline, PubMed, Embase, Bireme and Google Scholar without restrictions until July 2013. Randomized trials, human cohort clinical studies or case series with a control group on the use of PRP in tendons, ligaments or articular lesions were included. Equine clinical studies on the same topics were included inde...
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...
Paillot R, Hannant D, Kydd JH, Daly JM.Equine influenza virus is a leading cause of respiratory disease in the horse. Equine influenza vaccines containing inactivated virus were first developed in the 1960s. Despite their intensive use, equine influenza outbreaks still continue to occur and therefore new strategies of vaccination are necessary to improve vaccine efficacy. Numerous methods of vaccination have been evaluated and commercialised in the horse, the most recent being the cold-adapted influenza virus and poxvirus-based vaccines. As a large animal model, the horse is also a useful species in which to evaluate the potential ...
Fortier LA, Chapman HS, Pownder SL, Roller BL, Cross JA, Cook JL, Cole BJ.Microfracture (MFx) remains a dominant treatment strategy for symptomatic articular cartilage defects. Biologic scaffold adjuncts, such as particulated allograft articular cartilage (BioCartilage) combined with platelet-rich plasma (PRP), offer promise in improving clinical outcomes as an adjunct to MFx. To evaluate the safety, biocompatibility, and efficacy of BioCartilage and PRP for cartilage repair in a preclinical equine model of full-thickness articular cartilage loss. Controlled laboratory study. Two 10-mm-diameter full-thickness cartilage defects were created in 5 horses in the trochle...
Strauss EJ, Goodrich LR, Chen CT, Hidaka C, Nixon AJ.Chondral defects may lead to degradative changes in the surrounding cartilage, predisposing patients to developing osteoarthritis. Objective: To quantify changes in the biomechanical and biochemical properties of the articular cartilage adjacent to chondral defects after experimental defect repair. Methods: Controlled laboratory study. Methods: Specimens were harvested from tissue within (lesion), immediately adjacent to, and at a distance from (remote area) a full-thickness cartilage defect 8 months after cartilage repair with genetically modified chondrocytes expressing insulin-like growth f...
Lovati AB, Corradetti B, Lange Consiglio A, Recordati C, Bonacina E, Bizzaro D, Cremonesi F.Mesenchymal stem cells have been recently investigated for their potential use in regenerative medicine. Population of adult stem cells were recently identified in human and lab animal tendons, but no detailed investigations have been made in the equine species. The aim of our study is to identify a progenitor cell population from tendon tissue (TSPCs) in the horse superficial digital flexor tendon that are able to be highly clonogenic, to grow fast and to differentiate in different induced cell lineages as well as bone marrow derived progenitor cells (BM-MSCs). The hypothesis that TSPCs posse...
Carnevale EM.Reproductive aging and assisted reproduction are becoming progressively more relevant in human medicine. Research with human subjects is limited in many aspects, and consequently animal models may have considerable utility. Such models have provided insight into follicular function, oocyte maturation, and reproductive aging. However, models are often selected based on factors other than physiological or functional similarities. Although the mare has received limited attention as a model for reproduction in women, comparisons between these species indicate that the mare has many attributes of a...
Patterson-Kane JC, Rich T.Superficial digital flexor tendon (SDFT) injury in equine athletes is one of the most well-accepted, scientifically supported companion animal models of human disease (i.e., exercise-induced Achilles tendon [AT] injury). The SDFT and AT are functionally and clinically equivalent (and important) energy-storing structures for which no equally appropriate rodent, rabbit, or other analogues exist. Access to equine tissues has facilitated significant advances in knowledge of tendon maturation and aging, determination of specific exercise effects (including early life), and definition of some of the...
Peña FJ, O'Flaherty C, Ortiz RodrÃguez JM, MartÃn 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...
Bussche L, Harman RM, Syracuse BA, Plante EL, Lu YC, Curtis TM, Ma M, Van de Walle GR.The prevalence of impaired cutaneous wound healing is high and treatment is difficult and often ineffective, leading to negative social and economic impacts for our society. Innovative treatments to improve cutaneous wound healing by promoting complete tissue regeneration are therefore urgently needed. Mesenchymal stromal cells (MSCs) have been reported to provide paracrine signals that promote wound healing, but (i) how they exert their effects on target cells is unclear and (ii) a suitable delivery system to supply these MSC-derived secreted factors in a controlled and safe way is unavailabl...
Muir P, McCarthy J, Radtke CL, Markel MD, Santschi EM, Scollay MC, Kalscheur VL.The mechanisms that regulate functional adaptation of the articular ends of long bones are poorly understood. However, endochondral ossification of articular cartilage and modeling/remodeling of the subchondral plate and epiphyseal trabeculae are important components of the adaptive response. We performed a histologic study of the distal end of the third metacarpal/metatarsal bone of Thoroughbreds after bones were bulk-stained in basic fuchsin and calcified sections were prepared. The Thoroughbred racehorse is a model of an extreme athlete which experiences particularly high cyclic strains in ...
Paebst F, Piehler D, Brehm W, Heller S, Schroeck C, Tárnok A, Burk J.Horses are an approved large animal model for therapies of the musculoskeletal system. Especially for tendon disease where cell-based therapy is commonly used in equine patients, the translation of achieved results to human medicine would be a great accomplishment. Immunophenotyping of equine mesenchymal stromal cells (MSCs) remains the last obstacle to meet the criteria of the International Society for Cellular Therapy (ISCT) definition of human MSCs. Therefore, the surface antigen expression of CD 29, CD 44, CD 73, CD 90, CD 105, CD 14, CD 34, CD 45, CD 79α, and MHC II in equine MSCs from a...
Wutz G, Auer H, Nowotny N, Grosse B, Skern T, Kuechler E.Equine rhinoviruses (ERVs) are picornaviruses which cause a mild respiratory infection in horses. The illness resembles the common cold brought about by rhinoviruses in humans; however, the presence of a viraemia during ERV-1 infection, the occurrence of persistent infections and the physical properties are all more reminiscent of foot-and-mouth disease virus (FMDV). cDNA cloning and sequencing of the genomes of ERV-1 and ERV-2 between the poly(C) and poly(A) tracts showed that the serotypes are heterogeneous. Nevertheless, the genomic architecture of both serotypes is most similar to that of ...
