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.
Yu YY, Xu MS, Liang H, Wang HY, Yu CQ, Liu Q.Despite over 40 years of research on the human immunodeficiency virus type 1 (HIV-1) vaccine, we still lack a considerable progress. Equine infectious anemia virus (EIAV) is a lentivirus in the Retroviridae family, akin to HIV-1 in genome structure and antigenicity. EIA is an important infectious disease in equids, characterized by anemia, persistent infection, and repeated fevers. The EIAV attenuated vaccine in China is the only lentiviral vaccine used on a large scale. Elucidating the mechanism of waning and induction of protective immunity from this attenuated vaccine strain will provide a ...
Pozor MA, Benson SM, Macpherson ML, Kelleman AA.Transplantation of stem cells into dysfunctional testes is currently being investigated as a therapeutic option for men and stallions with advanced testicular degeneration. This series of "proof of concept" studies aimed to identify a safe and efficient method of inducing severe testicular degeneration to create an optimal equine recipient model for intratesticular stem cell transplantation (SCT). Two ex vivo and two in vivo experiments were conducted. At first, forty testes obtained from castrations were used to identify an effective therapeutic ultrasound (TUS) device and the protocol for ...
Mustonen AM, Lehmonen N, Paakkonen T, Raekallio M, Käkelä R, Niemelä T, Mykkänen A, Sihvo SP, Nieminen P.Individual fatty acids (FAs) and their derivatives (lipid mediators) with pro-inflammatory or dual anti-inflammatory and pro-resolving properties have potential to influence the health of joint tissues. Osteoarthritis (OA) is an age-associated chronic joint disease that can be featured with altered FA composition in the synovial fluid (SF) of human patients. The counts and cargo of extracellular vesicles (EVs), membrane-bound particles released by synovial joint cells and transporting bioactive lipids, can also be modified by OA. The detailed FA signatures of SF and its EVs have remained unexp...
Riveroll AL, Skyba-Lewin S, Lynn KD, Mubyeyi G, Abd-El-Aziz A, Kibenge FST, Kibenge MJT, Cohen AM, Esparza-Gonsalez B, McD￮ L, Montelpare WJ.Adipose-derived stem cells (ADSCs) are used in tissue regeneration therapies. The objective of this study is to identify stable reference genes (RGs) for use in gene expression studies in a characterized equine adipose-derived mesenchymal stem cell (EADMSC) differentiation model. ADSCs were differentiated into adipocytes (ADs) or osteoblasts (OBs), and the proteomes from these cells were analyzed by liquid chromatography tandem mass spectrometry. Proteins that were stably expressed in all three cells types were identified, and the mRNA expression stabilities for their corresponding genes were ...
Ciamillo SA, Pownder SL, Potter HG, Stefanovski D, Nixon AJ, Ortved KF.Injury of articular cartilage is common, and due to the poor intrinsic capabilities of chondrocytes, it can precipitate joint degradation and osteoarthritis (OA). Implantation of autologous chondrocytes into cartilaginous defects has been used to bolster repair. Accurate assessment of the quality of repair tissue remains challenging. This study aimed to investigate the utility of noninvasive imaging modalities, including arthroscopic grading and optical coherence tomography (OCT) for assessment of early cartilage repair (8 weeks), and MRI to determine long-term healing (8 months). Large (15 mm...
Gebremedhn S, Gad A, Ishak GM, Menjivar NG, Gastal MO, Feugang JM, Prochazka R, Tesfaye D, Gastal EL.Innumerable similarities in reproductive cyclicity and hormonal alterations highlight the considerable utility of the mare to study aspects of follicular dynamics and reproductive function in view of the largely constricted, human research subjects. The bi-directional communication between the growing oocyte and the surrounding somatic cells embodies the hallmark of mammalian follicular development, partially mediated by extracellular vesicles (EVs) encapsulated with microRNAs (miRNAs) and present in the follicular fluid (FF). Here, we aimed to decipher the dynamics of the miRNAs in EVs from e...
Prutton AM, Lenaghan HAH, Baillie S.Simulation in veterinary education is an important means of providing a safe, welfare-friendly way for students to hone their skills prior to performing procedures on live animals. Students may not get many chances to practice passing a nasogastric tube and checking for reflux in live horses during clinical rotations and extra-mural studies. A low-cost equine nasogastric intubation model was created at the University of Surrey, allowing students to practice passing a tube and checking for reflux. Thirty-two equine veterinarians evaluated the model for realism, and its potential usefulness in t...
Simonin EM, Babasyan S, Tarsillo J, Wagner B.IgE+ plasmablasts develop following allergen exposure and B cell activation. They secrete IgE and therefore are directly linked to maintain the mechanisms of IgE-mediated allergies. Here, we show that the presence of IgE+ plasmablasts in peripheral blood not only coincides with clinical allergy, but also predicts the upcoming development of clinical disease. Using an equine model of naturally occurring allergy, we compared the timing of allergen exposure, arrival of IgE+ plasmablasts in peripheral blood, and onset of clinical disease. We found that IgE+ plasmablasts predict the development of ...
Xing J, Qi X, Liu G, Li X, Gao X, Bou G, Bai D, Zhao Y, Du M, Dugarjaviin M, Zhang X.In response to muscle injury, muscle stem cells are stimulated by environmental signals to integrate into damaged tissue to mediate regeneration. L-leucine (L-leu), a branched-chain amino acid (BCAA) that belongs to the essential amino acids (AAs) of the animal, has gained global interest on account of its muscle-building and regenerating effects. The present study was designed to investigate the impact of L-leu exposure to promote the proliferation of equine skeletal muscle satellite cells (SCs) on the regulation of RNA networks, including mRNA, long non-coding RNA (lncRNA), covalently closed...
Suvá M, Arnold VH, Wiedenmann EA, Jordan R, Galvagno E, Martínez M, Vichera GD.Somatic cell nuclear transfer (SCNT) is an asexual reproductive technique where cloned offspring contain the same genetic material as the original donor. Although this technique preserves the sex of the original animal, the birth of sex-reversed offspring has been reported in some species. Here, we report for the first time the birth of a female foal generated by SCNT of a male nuclear donor. After a single SCNT procedure, 16 blastocysts were obtained and transferred to eight recipient mares, resulting in the birth of two clones: one male and one female. Both animals had identical genetic prof...
Granello ME, Weatherall KM, Lutter JD, Beard WL. The aim of this study was to compare the deflection distance, deflection angle and pre-loading sub-bandage pressure of a transverse, mid-metacarpal fracture in an equine cadaver limb when loaded in bending while stabilized with either a Robert Jones Bandage (RJB) or a single-stack bandage (SS), each containing two orthogonal splints. Methods: In an ex vivo experimental study, forelimb pairs from eight horses were collected, and one forelimb from each pair was assigned to either the SS or RJB groups. A transverse osteotomy was performed at the midpoint of the metacarpus. After bandaging, ...
Ginther OJ.The mechanism for selection of the future dominant or ovulatory follicle in mares involves a relatively abrupt separation in growth rates between the future dominant follicle and several subordinate follicles and is termed diameter deviation. The event is used to illustrate that a coordinated complex of many follicular, hormonal, and biochemical factors interact and interbalance during a single physiological mechanism. For example, a positive effect of follicle stimulating hormone (FSH) on development of all follicles during the growing phase can later involve a positive effect of luteinizing ...
Pezzanite LM, Chow L, Phillips J, Griffenhagen GM, Moore AR, Schaer TP, Engiles JB, Werpy N, Gilbertie J, Schnabel LV, Antczak D, Miller D, Dow S....Rapid development of antibiotic resistance necessitates advancement of novel therapeutic strategies to treat infection. Mesenchymal stromal cells (MSC) possess antimicrobial and immunomodulatory properties, mediated through antimicrobial peptide secretion and recruitment of innate immune cells including neutrophils and monocytes. TLR-3 activation of human, canine and equine MSC has been shown to enhance bacterial killing and clearance in vitro, in rodent Staphylococcal biofilm infection models and dogs with spontaneous multi-drug-resistant infections. The objective of this study was to determi...
Hainisch EK, Jindra C, Reicher P, Miglinci L, Brodesser DM, Brandt S.Equine sarcoids are common, locally aggressive skin tumors induced by bovine papillomavirus types 1, 2, and possibly 13 (BPV1, BPV2, BPV13). Current in vitro models do not mimic de novo infection. We established primary fibroblasts from horse skin and succeeded in infecting these cells with native BPV1 and BPV2 virions. Subsequent cell characterization was carried out by cell culture, immunological, and molecular biological techniques. Infection of fibroblasts with serial 10-fold virion dilutions (2 × 10-20 virions) uniformly led to DNA loads settling at around 150 copies/cell after four pass...
Dobler D, Gerber M, Schmidts TM, Runkel F, Schlupp P.Human nail diseases, mostly caused by fungal infections, are common and difficult to treat. The development and testing of new drugs and drug delivery systems for the treatment of nail diseases is often limited by the lack of human nail material for permeation studies. Animal material is frequently used, but there are only few comparative data on the human nail plate, and there is neither a standardized test design nor a nail bed analogue to study drug uptake into the nail. In this study, a new permeation device was developed for permeation studies, and the permeation behavior of three model s...
Cassano JM, Marycz K, Horna M, Nogues MP, Morgan JM, Herrmann DB, Galuppo LD, Vapniarsky N.No current treatments available halt osteoarthritis progression in horses or humans. Intra-articular injection of mitochondria is a novel treatment that has the potential to improve cell metabolism and decrease inflammation, but safety of this treatment has yet to be established in the horse. Autologous blood-derived mitochondria isolated using a commercially available kit were injected into the left carpus joint of 3 horses which were monitored for 28 days. Horses received physical examinations, video recorded gait evaluations, joint diameter measurement, synovial fluid collection, and blood ...
Górski K, Borowska M, Stefanik E, Polkowska I, Turek B, Bereznowski A, Domino M.Dental disorders are a serious health problem in equine medicine, their early recognition benefits the long-term general health of the horse. Most of the initial signs of Equine Odontoclastic Tooth Resorption and Hypercementosis (EOTRH) syndrome concern the alveolar aspect of the teeth, thus, the need for early recognition radiographic imaging. This study is aimed to evaluate the applicability of entropy measures to quantify the radiological signs of tooth resorption and hypercementosis as well as to enhance radiographic image quality in order to facilitate the identification of the signs of E...
Wotman KL, Chow L, Martabano B, Pezzanite LM, Dow S.Ocular surface squamous neoplasia (OSSN) is the major cause of corneal cancer in man and horses worldwide, and the prevalence of OSSN is increasing due to greater UVB exposure globally. Currently, there are no approved treatments for OSSN in either species, and most patients are managed with surgical excision or off-label treatment with locally injected interferon alpha, or topically applied cytotoxic drugs such as mitomycin C. A more broadly effective and readily applied immunotherapy could exert a significant impact on management of OSSN worldwide. We therefore evaluated the effectiveness of...
Dechêne L, Colin M, Demazy C, Fransolet M, Niesten A, Arnould T, Serteyn D, Dieu M, Renard P.Osteoarthritis (OA) is a highly prevalent joint degenerative disease for which therapeutic treatments are limited or invasive. Cell therapy based on mesenchymal stem/stromal cells (MSCs) is therefore seen as a promising approach for this disease, in both human and horses. As the regenerative potential of MSCs is mainly conferred by paracrine function, the goal of this study was to characterize the secreted proteins of muscle-derived MSCs (mdMSCs) in an in vitro model of OA to evaluate the putative clinical interest of mdMSCs as cell therapy for joint diseases like osteoarthritis. An equine ost...
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...
Jayathilake WMNK, Furr M, Risco C, Lacombe VA.Similar to human diabetes, equine metabolic syndrome (EMS) causes insulin dysregulation leading to debilitating sequela including laminitis. The pathophysiological mechanisms underlying EMS and laminitis are not well known. Therefore, using an insulin-resistant equine model, we hypothesized that insulin dysregulation induces an increased expression of inflammatory proteins in a tissue specific manner. Two groups of horses (n = -5/group) were categorized as insulin-resistant (IR) or insulin-sensitive (IS), using a frequently sampled intra-venous glucose tolerance test. Biopsies from skeletal ...
Thampi P, Samulski RJ, Grieger JC, Phillips JN, McIlwraith CW, Goodrich LR.With an intrinsically low ability for self-repair, articular cartilage injuries often progress to cartilage loss and joint degeneration resulting in osteoarthritis (OA). Osteoarthritis and the associated articular cartilage changes can be debilitating, resulting in lameness and functional disability both in human and equine patients. While articular cartilage damage plays a central role in the pathogenesis of OA, the contribution of other joint tissues to the pathogenesis of OA has increasingly been recognized thus prompting a whole organ approach for therapeutic strategies. Gene therapy metho...
Gobato MLM, Segabinazzi LGTM, Scheeren VFC, Bandeira RS, Freitas-Dell'Aqua CP, Dell'Aqua JA, Papa FO.Artificial insemination using cooled-transported semen has marked importance in equine breeding programs around the world, and the high value of mules has generated avid interest in donkey semen biotechnology. However, donkey semen cools poorly in commercially available equine extenders. Therefore, this study aimed to develop approaches to improve the ability of donkey semen to tolerate cooling. Ejaculates of seven donkeys (n = 21) were cooled at 5°C for 48 h in three different extenders (milk-based, SM; sodium caseinate-based, SC; or egg yolk-based, EY) in the presence or absence of seminal ...
Cahalan SD, Perkins JD, Boehm I, Jones RA, Gillingwater TH, Piercy RJ.Morphological study of the neuromuscular junction (NMJ), a specialised peripheral synapse formed between a lower motor neuron and skeletal muscle fibre, has significantly contributed to the understanding of synaptic biology and neuromuscular disease pathogenesis. Rodent NMJs are readily accessible, and research into conditions such as amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease (CMT), and spinal muscular atrophy (SMA) has relied heavily on experimental work in these small mammals. However, given that nerve length dependency is an important feature of many peripheral neurop...
Mandal S, Denham MM, Spencer SJ, Denham J.Ageing causes a gradual deterioration of bodily functions and telomere degradation. Excessive telomere shortening leads to cellular senescence and decreases tissue vitality. Six proteins, called shelterin, protect telomere integrity and control telomere length through telomerase-dependent mechanisms. Exercise training appears to maintain telomeres in certain somatic cells, although the underlying molecular mechanisms are incompletely understood. Here, we examined the influence of a single bout of vigorous exercise training on leukocyte telomerase reverse transcriptase (TERT) and shelterin gene...
Feugang JM, Ishak GM, Eggert MW, Arnold RD, Rivers OS, Willard ST, Ryan PL, Gastal EL.Despite the progress in assisted reproductive techniques, there is still a lack of rapid and minimally invasive in situ approaches for further enhancements of female fertility. Therefore, we synthesized clinically relevant liposome nanoparticles for ovarian intrafollicular injection to allow in vivo cellular imaging for future drug delivery, using the mare as an animal model. Ovarian follicles of living mares were injected in vivo with fluorescently labeled liposomes. Samples of the follicular wall (mural granulosa, theca interna, and theca externa), granulosa cells, and follicular fluid wer...
Hayden LR, Stoker AM, Johnson PJ, McCracken MJ.To determine the following: (1) whether an irrigation solution that is hyperosmolar (HYPER) relative to synovial fluid decreases tissue extravasation during an arthroscopic protocol when compared to a relatively hypoosmolar solution, (2) the safety of a HYPER solution based on viability of joint tissues following joint irrigation, and (3) if the use of a HYPER solution decreases water content in stifle joint tissue. Methods: 8 adult horses. Methods: A prospective, blinded, randomized controlled trial was performed to compare lactated Ringer's solution (LRS; 273 mOsm/L) and a HYPER (600 mOsm/L)...
Hoffmann ALC, Hauck SM, Deeg CA, Degroote RL.In the pathophysiology of autoimmune-mediated uveitis, granulocytes have emerged as possible disease mediators and were shown to be pre-activated in equine recurrent uveitis (ERU), a spontaneous disease model. We therefore used granulocytes from ERU horses to identify early molecular mechanisms involved in this dysregulated innate immune response. Primary granulocytes from healthy and ERU horses were stimulated with IL8, and cellular response was analyzed with differential proteomics, which revealed significant differences in protein abundance of 170 proteins in ERU. Subsequent ingenuity pathw...
Cain JL, Nielsen MK.The equine ascarids, Parascaris spp., are important nematode parasites of juvenile horses and were historically model organisms in the field of cell biology, leading to many important discoveries, and are used for the study of chromatin diminution. In veterinary parasitology, Parascaris spp. are important not only because they can cause clinical disease in young horses but also because they are the only ascarid parasites to have developed widespread anthelmintic resistance. Despite this, much of the general biology and mechanisms of anthelmintic resistance are poorly understood. This review co...
Klier J, Fuchs S, Winter G, Gehlen H.Severe equine asthma is the most common globally widespread non-infectious equine respiratory disease (together with its mild and moderate form), which is associated with exposure to hay dust and mold spores, has certain similarities to human asthma, and continues to represent a therapeutic problem. Immunomodulatory CpG-ODN, bound to gelatin nanoparticles as a drug delivery system, were successfully administered by inhalation to severe equine asthmatic patients in several studies. It was possible to demonstrate a significant, sustained, and allergen-independent one-to-eight-week improvement in...
Vargas A, Boivin R, Cano P, Murcia Y, Bazin I, Lavoie JP.Severe neutrophilic asthma is poorly responsive to glucocorticosteroids (GC). Neutrophil extracellular traps (NETs) within the lungs have been associated with the severity of airway obstruction and inflammation in asthma, and were found to be unaffected by GC in vitro. As IL-17 is overexpressed in neutrophilic asthma and contributes to steroid insensitivity in different cell types, we hypothesized that NETs formation in asthmatic airways would be resistant to GC through an IL-17 mediated pathway. Six neutrophilic severe asthmatic horses and six healthy controls were studied while being treated...
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...
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 ...
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 ...
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...
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...
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...
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...
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...
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...
Capomaccio S, Vitulo N, Verini-Supplizi A, Barcaccia G, Albiero A, D'Angelo M, Campagna D, Valle G, Felicetti M, Silvestrelli M, Cappelli K.The horse is an optimal model organism for studying the genomic response to exercise-induced stress, due to its natural aptitude for athletic performance and the relative homogeneity of its genetic and environmental backgrounds. Here, we applied RNA-sequencing analysis through the use of SOLiD technology in an experimental framework centered on exercise-induced stress during endurance races in equine athletes. We monitored the transcriptional landscape by comparing gene expression levels between animals at rest and after competition. Overall, we observed a shift from coding to non-coding regio...
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 ...
Ginther OJ, Gastal EL, Gastal MO, Bergfelt DR, Baerwald AR, Pierson RA.Deviation in growth rates of the follicles of the ovulatory wave begins at the end of a common growth phase and is characterized by continued growth of the developing dominant follicle (F1) and regression of the largest subordinate follicle (F2). Follicle diameters during an interovulatory interval were compared between 30 mares and 30 women, using similar methods for collecting and analyzing data. Follicles were tracked and measured daily by ultrasonography. Diameter at follicle emergence (mares, 13 mm; women, 6 mm) and the required minimal attained diameter for assessment of follicles (mares...
Nunamaker DM, Butterweck DM, Provost MT.The North American Thoroughbred racehorse was chosen as a model to study the pathogenesis of fatigue failure of bone. This species has a high incidence of spontaneous fatigue failure of bone (bucked shins) during its early training. In vivo strain gauge studies of the third metacarpal bone of four young racehorses running at racing speeds showed high principal compressive strains [-4,841 +/- 572 (SD) microstrain] while two older horses had lower principal compressive strains (-3,317 microstrain measured at racing speed, -3,250 microstrain extrapolated from a slower speed run). Previously repor...
Mancini IAD, Schmidt S, Brommer H, Pouran B, Schäfer S, Tessmar J, Mensinga A, van Rijen MHP, Groll J, Blunk T, Levato R, Malda J, van Weeren PR.Recent research has been focusing on the generation of living personalized osteochondral constructs for joint repair. Native articular cartilage has a zonal structure, which is not reflected in current constructs and which may be a cause of the frequent failure of these repair attempts. Therefore, we investigated the performance of a composite implant that further reflects the zonal distribution of cellular component both in vitro and in vivo in a long-term equine model. Constructs constituted of a 3D-printed poly(ϵ-caprolactone) (PCL) bone anchor from which reinforcing fibers protruded into ...
Heinzerling LM, Feige K, Rieder S, Akens MK, Dummer R, Stranzinger G, Moelling K.Preclinical studies investigating new therapeutic principles against melanoma are presently being carried out in mouse models; however, these are not optimal. Here we describe a novel animal model using gray horses. These animals spontaneously develop metastatic melanoma that resembles human disease and is thus highly relevant for preclinical studies testing new immunotherapy protocols. We found that injection of plasmid DNA coding for the human cytokine interleukin 12 into established metastases induced significant regression in all 12 treated lesions in a total of 7 horses. Complete disappea...
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...
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...
Leclere M, Lavoie-Lamoureux A, Gélinas-Lymburner E, David F, Martin JG, Lavoie JP.Recent studies suggest that airway smooth muscle remodeling is an early event in asthma, but whether it remains a dynamic process late in the course of the disease is unknown. Moreover, little is known about the effects of an antigenic exposure on chronically established smooth muscle remodeling. We measured the effects of antigenic exposure on airway smooth muscle in the central and peripheral airways of horses with heaves, a naturally occurring airway disease that shares similarities with chronic asthma. Heaves-affected horses (n = 6) and age-matched control horses (n = 5) were kept on pastu...
Clutterbuck AL, Smith JR, Allaway D, Harris P, Liddell S, Mobasheri A.This study employed a targeted high-throughput proteomic approach to identify the major proteins present in the secretome of articular cartilage. Explants from equine metacarpophalangeal joints were incubated alone or with interleukin-1beta (IL-1β, 10ng/ml), with or without carprofen, a non-steroidal anti-inflammatory drug, for six days. After tryptic digestion of culture medium supernatants, resulting peptides were separated by HPLC and detected in a Bruker amaZon ion trap instrument. The five most abundant peptides in each MS scan were fragmented and the fragmentation patterns compared to m...
Garcia-Tapia D, Loiacono CM, Kleiboeker SB.A cell model of primary monocytes and other mononuclear cells isolated from equine blood was used to study the kinetics of West Nile virus (WNV) replication in a natural host. West Nile virus has emerged on the North American continent as a significant cause of morbidity and mortality in a wide range of avian and mammalian species. While other flaviviruses are known to infect monocytes and lymphocytes, the ability of WNV to productively replicate in specific immune cells of peripheral blood has not been assessed. In this study, enriched populations of monocytes and lymphocytes as well as purif...
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...
Harman RM, Patel RS, Fan JC, Park JE, Rosenberg BR, Van de Walle GR.The efficacy of mesenchymal stromal cell (MSC) therapy is thought to depend on the intrinsic heterogeneity of MSC cultures isolated from different tissue sources as well as individual MSCs isolated from the same tissue source, neither of which is well understood. To study this, we used MSC cultures isolated from horses. The horse is recognized as a physiologically relevant large animal model appropriate for translational MSC studies. Moreover, due to its large size the horse allows for the simultaneous collection of adequate samples from multiple tissues of the same animal, and thus, for the u...
Frisbie DD, Bowman SM, Colhoun HA, DiCarlo EF, Kawcak CE, McIlwraith CW.To evaluate a technique of autologous chondrocyte implantation (ACI) similar to the other techniques using cell-seeded resorbable collagen membranes in large articular defects. Methods: Autologous cartilage was harvested arthroscopically from the lateral trochlear ridge of the femur in fifteen 3-year-old horses. After culture and expansion of chondrocytes the newly created ACI construct (autologous chondrocytes cultured expanded, seeded on a collagen membrane, porcine small intestine submucosa) was implanted into 15mm defects on the medial trochlear ridge of the femur in the opposite femoropat...
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 ...
Maumus M, Roussignol G, Toupet K, Penarier G, Bentz I, Teixeira S, Oustric D, Jung M, Lepage O, Steinberg R, Jorgensen C, Noel D.Mesenchymal stem cells isolated from adipose tissue (ASC) have been shown to influence the course of osteoarthritis (OA) in different animal models and are promising in veterinary medicine for horses involved in competitive sport. The aim of this study was to characterize equine ASCs (eASCs) and investigate the role of interferon-gamma (IFNγ)-priming on their therapeutic effect in a murine model of OA, which could be relevant to equine OA. Methods: ASC were isolated from subcutaneous fat. Expression of specific markers was tested by cytometry and RT-qPCR. Differentiation potential was evaluat...
Watson Levings RS, Broome TA, Smith AD, Rice BL, Gibbs EP, Myara DA, Hyddmark EV, Nasri E, Zarezadeh A, Levings PP, Lu Y, White ME, Dacanay EA....Toward the treatment of osteoarthritis (OA), the authors have been investigating self-complementary adeno-associated virus (scAAV) for intra-articular delivery of therapeutic gene products. As OA frequently affects weight-bearing joints, pharmacokinetic studies of scAAV gene delivery were performed in the joints of the equine forelimb to identify parameters relevant to clinical translation in humans. Using interleukin-1 receptor antagonist (IL-1Ra) as a secreted therapeutic reporter, scAAV vector plasmids containing codon-optimized cDNA for equine IL-1Ra (eqIL-1Ra) were generated, which produc...
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...
Diloksumpan P, Bolaños RV, Cokelaere S, Pouran B, de Grauw J, van Rijen M, van Weeren R, Levato R, Malda J.The clinical translation of three-dimensionally printed bioceramic scaffolds with tailored architectures holds great promise toward the regeneration of bone to heal critical-size defects. Herein, the long-term in vivo performance of printed hydrogel-ceramic composites made of methacrylated-oligocaprolactone-poloxamer and low-temperature self-setting calcium-phosphates is assessed in a large animal model. Scaffolds printed with different internal architectures, displaying either a designed porosity gradient or a constant pore distribution, are implanted in equine tuber coxae critical size defec...
