The study of cells in horses encompasses the examination of various cell types and their functions within the equine body. Cells are the basic structural and functional units of life, and in horses, they contribute to numerous physiological processes, including growth, repair, and immune responses. Different cell types, such as red blood cells, white blood cells, and muscle cells, each perform specific roles that are vital for maintaining the health and homeostasis of the horse. This topic includes research on cellular mechanisms, cellular responses to disease or injury, and the application of cellular biology in equine medicine. This page compiles peer-reviewed research studies and scholarly articles that explore the structure, function, and significance of cells in equine biology and health.
O'Brien TJ, Hollinshead F, Goodrich LR.Osteoarthritis (OA) is a common joint disease affecting humans and horses, resulting in significant morbidity, financial expense, and loss of athletic use. While the pathogenesis is incompletely understood, inflammation is considered crucial in the development and progression of the disease. Mesenchymal stromal cells (MSCs) have received increasing scientific attention for their anti-inflammatory, immunomodulatory, and pro-regenerative effects. However, there are concerns about their ability to become a commercially available therapeutic. Extracellular vesicles (EVs) are now recognized to play...
Etcharren V, Mouguelar H, Aguilar Valenciano JJ.Telocytes (TCs), a recently discovered special type of stromal cells, have been identified in many organs of many species, including the female and male reproductive system, with proposed multiple potential bio-functions such as homeostasis, immunomodulation, tissue remodeling and regeneration, embryogenesis, angiogenesis and even tumorigenesis. The aim of this study was to investigate the existence, and characteristics of telocytes in normal equine oviduct. To identify them, we used routine light microscopy, non-conventional light microscopy (NCLM), transmission electron microscopy (TEM), and...
Marsico TV, Valente RS, Annes K, Oliveira AM, Silva MV, Sudano MJ.A wide-ranging review study regarding the molecular characterization of the first cell lineages of the developmental embryo is lacking, especially for the primary events during earliest differentiation which leads to the determination of cellular fate. Here, a systematic review and meta-analysis were conducted according to PRISMA guidelines. MEDLINE-PubMed was searched based on an established search strategy through April 2021. Thirty-six studies fulfilling the inclusion criteria were subjected to qualitative and quantitative analysis. Among the studies, 50 % (18/36) used mice as an animal mod...
Andrietti ALP, Durgam SS, Naumann B, Stewart M.Mesenchymal stem cells are characterized by their capacities for extensive proliferation through multiple passages and, classically, tri-lineage differentiation along osteogenic, chondrogenic and adipogenic lineages. This study was carried out to compare osteogenesis in equine bone marrow-, synovium- and adipose-derived cells, and to determine whether osteogenic capacity is reflected in the basal expression of the critical osteogenic transcription factors Runx2 and Osterix. Unassigned: Bone marrow, synovium and adipose tissue was collected from six healthy 2-year-old horses. Cells were isolate...
Bourebaba L, Serwotka-Suszczak A, Pielok A, Sikora M, Mularczyk M, Marycz K.Equine metabolic syndrome (EMS) is a multifactorial pathology gathering insulin resistance, low-grade inflammation and past or chronic laminitis. Among the several molecular mechanisms underlying EMS pathogenesis, increased negative insulin signalling regulation mediated by protein tyrosine phosphatase 1 B (PTP1B) has emerged as a critical axis in the development of liver insulin resistance and general metabolic distress associated to increased ER stress, inflammation and disrupted autophagy. Thus, the use of PTP1B selective inhibitors such as MSI-1436 might be considered as a golden therapeut...
Belacic ZA, Sullivan SN, Rice HC, Durgam SS.To investigate the effects of interleukin-1β (IL-1β) and methylprednisolone acetate (MPA) on equine intrabursal deep digital flexor tendon (DDFT) and navicular bone fibrocartilage (NBF) cells in vitro. Methods: Third passage DDFT and NBF cells from 5 healthy donor horses ages 11-17 years euthanized for reasons unrelated to musculoskeletal conditions. Methods: Aggregate cultures were incubated with culture medium alone (control), 10 ng/mL IL-1β, 10 ng/mL IL-1β + 0.05 mg/mL MPA, or 10 ng/mL IL-1β + 0.5 mg/mL MPA for 24 hours. Extracellular matrix (ECM) gene expressions were assessed via rea...
Kang H, Lee GKC, Bienzle D, Arroyo LG, Sears W, Lillie BN, Beeler-Marfisi J.Alveolar macrophages (AMs) are the predominant innate immune cell in the distal respiratory tract. During inflammatory responses, AMs may be supplemented by blood monocytes, which differentiate into monocyte-derived macrophages (MDMs). Macrophages play important roles in a variety of common equine lower airway diseases, including severe equine asthma (SEA). In an experimental model, an inhaled mixture of Aspergillus fumigatus spores, lipopolysaccharide, and silica microspheres (FLS), induced SEA exacerbation in susceptible horses. However, whether equine AMs and MDMs have differing immunopheno...
Panizzi L, Dittmer KE, Vignes M, Doucet JS, Gedye K, Waterland MR, Rogers CW, Sano H, McIlwraith CW, Riley CB.Biomarkers for osteoarthritis (OA) in horses have been extensively investigated, but translation into clinical use has been limited due to cost, limited sensitivity, and practicality. Identifying novel biomarkers that overcome these limitations could facilitate early diagnosis and therapy. This study aimed to compare the concentrations of synovial fluid (SF) and plasma cell-free DNA (cfDNA) over time in control horses with those with induced carpal OA. Following an established model, unilateral carpal OA was induced in 9 of 17 healthy Thoroughbred fillies, while the remainder were sham-operate...
Elliott J, Bailey SR.Equine laminitis has both fascinated and frustrated veterinary researchers and clinicians for many years. The recognition that many ponies suffering from pasture-associated laminitis have an insulin-dysregulated phenotype (endocrinopathic laminitis, EL) and that prolonged insulin and glucose infusions can experimentally induce laminar pathology and functional failure are seminal discoveries in this field. Researchers have studied the molecular basis for disease pathogenesis in models of EL, sepsis-related laminitis and supporting limb laminitis and generated much data over the last 15 years....
Heilen LB, Roßgardt J, Dern-Wieloch J, Vogelsberg J, Staszyk C.The lifelong eruption places a great demand on the dental pulp and periodontal ligament (PDL) of horse teeth. Cells within the pulp and PDL seem to play a key role during this remodeling. Unassigned: In this study, we isolated and cultivated MSCs (medicinal signaling cells) from dental pulp, PDL and retrobulbar fat of four horses. Subsequently, we analyzed them by flow cytometry and immunohistochemistry to determine and compare their characteristics. In addition, we localized these cells within the tissue structure via immunohistochemistry of histological sections. For these analyses, several ...
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...
Persistent post-breeding induced endometritis (PPBIE) is considered a major cause of subfertility in mares. It consists of persistent or delayed uterine inflammation in susceptible mares. There are many options for the treatment of PPBIE, but in this study, a novel approach aimed at preventing the onset of PPBIE was investigated. Stallion semen was supplemented with extracellular vesicles derived from amniotic mesenchymal stromal cells (AMSC-EVs) at the time of insemination to prevent or limit the development of PPBIE. Before use in mares, a dose-response curve was produced to evaluate the eff...
Zamith Cunha R, Zannoni A, Salamanca G, De Silva M, Rinnovati R, Gramenzi A, Forni M, Chiocchetti R.The metacarpophalangeal joint undergoes enormous loading during locomotion and can therefore often become inflamed, potentially resulting in osteoarthritis (OA). There are studies indicating that the endocannabinoid system (ECS) modulates synovium homeostasis, and could be a promising target for OA therapy. Some cannabinoid receptors, which modulate proliferative and secretory responses in joint inflammation, have been functionally identified in human and animal synovial cells. Unassigned: To characterize the cellular distribution of the cannabinoid receptors 1 (CB1R) and 2 (CB2R), and the can...
Umair M, Beitsma M, de Ruijter-Villani M, Deelen C, Herrera C, Stout TAE, Claes A.The cryotolerance of equine blastocysts larger than 300 μm can be improved by aspirating blastocoele fluid prior to vitrification; however, it is not known whether blastocoele aspiration also enables successful slow-freezing. The aim of this study was therefore to determine whether slow-freezing of expanded equine embryos following blastocoele collapse was more or less damaging than vitrification. Grade 1 blastocysts recovered on day 7 or 8 after ovulation were measured (>300-550 μm, n = 14 and > 550 μm, n = 19) and blastocoele fluid was aspirated prior to slow-freezing in 10...
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...
Nakken G, Kirk J, Fjordbakk CT.Autologous conditioned serum (ACS), i.e serum enriched with anti-inflammatory cytokines and growth factors, is a popular orthobiologic therapy used in equine practice. Costly specialized tubes containing glass beads are commonly used for ACS production. The objective of this in vitro study was to compare cytokine and growth factor levels in equine serum after incubation in three different tubes: commercial plastic ACS tubes (COMM); sterile 50 ml plastic centrifugation tubes (CEN); and 10 ml plastic vacutainer tubes (VAC). Blood from 15 healthy horses was incubated in the different tubes at 3...
Jammes M, Contentin R, Cassé F, Galéra P.Osteoarthritis (OA) is a degenerative disease that eventually leads to the complete degradation of articular cartilage. Articular cartilage has limited intrinsic capacity for self-repair and, to date, there is no curative treatment for OA. Humans and horses have a similar articular cartilage and OA etiology. Thus, in the context of a One Health approach, progress in the treatment of equine OA can help improve horse health and can also constitute preclinical studies for human medicine. Furthermore, equine OA affects horse welfare and leads to significant financial losses in the equine industry....
Teti G, Mazzotti E, Gatta V, Chiarini F, Alfieri ML, Falconi M.Osteoarthritis (OA) is described as a chronic degenerative disease characterized by the loss of articular cartilage. Senescence is a natural cellular response to stressors. Beneficial in certain conditions, the accumulation of senescent cells has been implicated in the pathophysiology of many diseases associated with aging. Recently, it has been demonstrated that mesenchymal stem/stromal cells isolated from OA patients contain many senescent cells that inhibit cartilage regeneration. However, the link between cellular senescence in MSCs and OA progression is still debated. In this study, we ai...
Alshahrani SH, Alameri AA, Kahar F, Alexis Ramírez-Coronel A, Fadhel Obaid R, Alsaikhan F, Zabibah RS, Qasim QA, Altalbawy FMA, Fakri Mustafa Y....Recently in vivo and in vitro studies have provided evidence establishing the significance of microRNAs (miRNAs) in both physiological and pathological conditions. In this regard, the role of miRNA-128 (miR-128) in health and diseases has been found, and its critical regulatory role in the context of some viral diseases has been recently identified. For instance, it has been found that miR-128 can serve as an antiviral mediator and significantly limit the replication and dissemination of human immunodeficiency virus type 1 (HIV-1). Besides, it has been noted that poliovirus receptor-related 4 ...
Kaneps AJ.Regenerative medicine therapies have become significant tools for treatment of joint, soft tissue, and a variety of other conditions in animals and humans. Regenerative medicine aims to restore form and function of injured tissues using the body's own resources such as cells, fluids (ie, plasma and serum), and their resulting anti-inflammatory and prohealing cytokines. Platelet-rich plasma and other hemoderivatives have application for joint disorders such as osteoarthritis, cartilage injury, synovitis, and soft tissue injuries. These therapies achieve anti-inflammatory and healing effects wit...
Castro-Cuellar G, Cremer J, Liu CC, Queiroz-Williams P, Hampton C, Leise BS.To investigate the cytotoxic effects of 2 different concentrations of buprenorphine and compare them with bupivacaine and morphine on healthy equine chondrocytes in vitro. Methods: Primary cultured equine articular chondrocytes from 3 healthy adult horses. Methods: Chondrocytes were exposed for 0 and 2 hours to the following treatments: media (CON; negative control); bupivacaine at 2.2 mg/mL (BUPI; positive control); morphine at 2.85 mg/mL (MOR); buprenorphine at 0.12 mg/mL (HBUPRE); or buprenorphine at 0.05 mg/mL (LBUPRE). Chondrocyte viability was assessed using live/dead staining, water-sol...
Quattrini C, Scalco R, Vernau W, Dini P, Aleman M.Cerebrospinal fluid (CSF) is highly labile and delayed processing might alter results of analysis. Objective: To determine the effects of time and addition of autologous serum on cytological evaluation of CSF. Methods: Ten client-owned adult horses requiring euthanasia. Methods: Prospective study. Serum and CSF were collected from each horse before and within 10 minutes after euthanasia. CSF samples were divided into 15 aliquots (2 mL each); 1 aliquot was submitted for routine CSF analysis within 60 minutes of collection. Four drops of autologous serum were added to 7 of the aliquots, and ...
Parrilla Hernández S, Franck T, Munaut C, Feyereisen É, Piret J, Farnir F, Reigner F, Barrière P, Deleuze S.Myeloperoxidase (MPO), as a marker of neutrophil activation, has been associated with equine endometritis. However, in absence of inflammation, MPO is constantly detected in the uterine lumen of estrous mares. The aim of this study was to characterize MPO in the uterus of mares under physiological conditions as a first step to better understand the role of this enzyme in equine reproduction. Total and active MPO concentrations were determined, by ELISA and SIEFED assay, respectively, in low-volume lavages from mares in estrus ( = 26), diestrus ( = 18) and anestrus ( = 8) in absence of endometr...
Marycz K, Bourebaba N, Serwotka-Suszczak A, Mularczyk M, Galuppo L, Bourebaba L.Equine metabolic syndrome (EMS) is recognized as one of the leading cause of health threatening in veterinary medicine worldwide. Recently, PTP1B inhibition has been proposed as an interesting strategy for liver insulin resistance reversion in both equines and humans, however as being a multifactorial disease, proper management of EMS horses further necessities additional interventional approaches aiming at repairing and restoring liver functions. In this study, we hypothesized that in vitro induction of Eq_ASCs hepatogenic differentiation will generate a specialized liver progenitor-like cell...
Elbrønd VS, Thomsen MB, Isaksen JL, Lunde ED, Vincenti S, Wang T, Tranum-Jensen J, Calloe K.The Purkinje fibers convey the electrical impulses at much higher speed than the working myocardial cells. Thus, the distribution of the Purkinje network is of paramount importance for the timing and coordination of ventricular activation. The Purkinje fibers are found in the subendocardium of all species of mammals, but some mammals also possess an intramural Purkinje fiber network that provides for relatively instantaneous, burst-like activation of the entire ventricular wall, and gives rise to an rS configuration in lead II of the ECG. To relate the topography of the horse heart and the dis...
Marr N, Zamboulis DE, Werling D, Felder AA, Dudhia J, Pitsillides AA, Thorpe CT. The interfascicular matrix (IFM; also known as the endotenon) is critical to the mechanical adaptations and response to load in energy-storing tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT). We hypothesized that the IFM is a tendon progenitor cell niche housing an exclusive cell subpopulation. Immunolabelling of equine superficial digital flexor tendon was used to identify the interfascicular matrix niche, localising expression patterns of CD31 (endothelial cells), Desmin (smooth muscle cells and pericytes), CD146 (interfascicular matrix cells) and LA...
Salinas C, Barriga K, Albornoz A, Alarcon P, Quiroga J, Uberti B, Sarmiento J, Henriquez C, Ehrenfeld P, Burgos RA, Moran G.Neutrophils display an array of biological functions including the formation of neutrophil extracellular traps (NETs), web-like structures specialized in trapping, neutralizing, killing and preventing microbial dissemination within the host. However, NETs contribute to a number of inflammatory pathologies, including severe equine asthma. Tamoxifen (TX) is a selective estrogen receptor modulator which belongs to the triphenylethyllenes group of molecules, and which is used as a treatment in all stages of estrogen-positive human breast cancer. Our previous results suggest that tamoxifen can modu...
Bone reportsJanuary 5, 2023
Volume 18 101653 doi: 10.1016/j.bonr.2023.101653
Grissom SK, Semevolos SA, Duesterdieck-Zellmer K.The objective of this study is to better understand the pathogenesis of early equine osteochondrosis (OC) by identifying differences in gene and protein expression of extracellular matrix components and regulators in normal and diseased cartilage and bone, focusing on the osteochondral junction and cells surrounding the cartilage canals. We expected to find an upregulation of matrix metalloproteinases and a decrease in extracellular matrix constituent expression along the osteochondral junction and cells surrounding the cartilage canals in OC samples. Paraffin-embedded osteochondral samples (6...
Gysens L, Depuydt E, Patruno M, Haspeslagh M, Spaas JH, Martens A.Sarcoids are the most common equine skin tumours Although they do not metastasize, they can be locally aggressive and cause significant clinical symptoms in affected horses. Despite being common, very little is known about the host immune response and the biological mechanisms underlying persistence and recurrence of equine sarcoids. The latter reflects the need for further research in this field. This in-vitro study used sarcoid explants from horses with naturally occurring sarcoids (n = 12) to evaluate the induction of a humoral immune response directed against equine sarcoid-derived bovin...
Blommaert D, Sergeant N, Delehedde M, Jouy N, Mitchell V, Franck T, Donnay I, Lejeune JP, Serteyn D.A-kinase anchor protein 4 (AKAP4) is playing a central role in flagellar structure, chemotaxis, capacitation and sperm motility. In mammals, AKAP4 is expressed during spermatogenesis. AKAP4 is synthesized as a precursor, proAKAP4, which is cleaved into mature AKAP4 during fibrous sheath assembly. The proAKAP4 is a good indicator of sperm quality in humans and boars. The aims of this work were to study the expression, the localization and the concentration of proAKAP4 and AKAP4 in equine semen, and to evaluate the possible correlation between the total and progressive motility and the concentra...
Whitworth DJ, Banks TA.There has been unprecedented interest in recent years in the use of stem cells as therapy for an array of diseases in companion animals. Stem cells have already been deployed therapeutically in a number of clinical settings, in particular the use of mesenchymal stem cells to treat osteoarthritis in horses and dogs. However, an assessment of the scientific literature highlights a marked disparity between the purported benefits of stem cell therapies and their proven abilities as defined by rigorously controlled scientific studies. Although preliminary data generated from clinical trials in huma...
Russell LD, Ren HP, Sinha Hikim I, Schulze W, Sinha Hikim AP.Morphometric studies were performed on 12 mammalian species (degu, dog, guinea pig, hamster, human, monkey, mouse, opossum, rabbit, rat, stallion, and woodchuck) to determine volume density percentage (Vv%), volume (V), and numerical density (Nv) of seminiferous tubule components, especially those related to the Sertoli cell, and to make species comparisons. For most species, measurements were taken both from stages where elongate spermatids were deeply embedded within the Sertoli cell and from stages near sperm release where elongate spermatids were in shallow crypts within the Sertoli cell. ...
Lange-Consiglio A, Lazzari B, Perrini C, Pizzi F, Stella A, Cremonesi F, Capra E.Cell-derived microvesicles (MVs) are a recently discovered mechanism of cell-to-cell communication. Our previous data show that MVs secreted by equine amniotic mesenchymal-derived cells (AMCs) are involved in downregulation of proinflammatory genes in lipopolysaccharide-stressed equine tendon and endometrial cells. The aim of the present study was to evaluate whether AMC-MVs contain selected microRNAs (miRNAs) involved in inflammation. Two pools of cells, derived from 3 amniotic membranes each, and their respective MVs were collected. Small RNAs were extracted and deep sequenced, followed by m...
Bonnefoy A, Romijn RA, Vandervoort PA, VAN Rompaey I, Vermylen J, Hoylaerts MF.Binding of von Willebrand factor (VWF) to platelet GPIbalpha and to collagen is attributed to VWF A1 and A3 domains, respectively. Objective: Using VWF, VWF lacking A1 (DeltaA1-VWF) or A3 (DeltaA3-VWF) and VWF with defective A3 (H1786A-VWF), in combination with recombinant A1 (residues 1262-1492) or A3 (residues 1671-1878), fused to glutathione-S-transferase (GST-A1 and GST-A3), we have re-investigated the role of A1 in platelet recruitment to surfaces of collagen. Results: In flow, measurable binding of DeltaA3-VWF occurred to horse tendon, but also to human type III collagen. GST-A1 and GST-...
Hoffman LH, Wooding FB.The cellular origin, structure, and function of trophoblastic giant cells (GC) and binucleate cells (BNC) are reviewed. Mammals in which these cells have received the greatest attention include rodents, rabbits, and humans (GCs), and ruminants and equids (BNCs). In almost all cases these cells arise from the cytotrophoblast. All are large cells and contain either two diploid nuclei (BNCs), multiple nuclei (human placental bed GCs), or single nuclei with amplified DNA content (rodent and rabbit GCs). Giant and binucleate cells typically exhibit the capacity for migration or invasion, although t...
Kleinheinz J, Jung S, Wermker K, Fischer C, Joos U.Current approaches in bone regeneration combine osteoconductive scaffolds with bioactive cytokines like BMP or VEGF. The idea of our in-vitro trial was to apply VEGF165 in gradient concentrations to an equine collagen carrier and to study pharmacological and morphological characteristics of the complex in a circulation model. Methods: Release kinetics of VEGF165 complexed in different quantities in a collagen matrix were determined in a circulation model by quantifying protein concentration with ELISA over a period of 5 days. The structural changes of the collagen matrix were assessed with lig...
Klohonatz KM, Cameron AD, Hergenreder JR, da Silveira JC, Belk AD, Veeramachaneni DN, Bouma GJ, Bruemmer JE.During early pregnancy, the conceptus and mare communicate to establish pregnancy. Cell-secreted vesicles (e.g., exosomes) have been reported in serum. Exosomes contain bioactive materials, such as miRNA, that can mediate cell responses. We hypothesized that a) exosomes are present in mare circulation and quantity varies with pregnancy status, b) exosomes contain miRNAs unique to pregnancy status, and c) miRNAs target pathways in endometrium based upon pregnancy status of the mare. First, serum samples were obtained from mares in a crossover design, with each mare providing samples from a preg...
Daly K, Al-Rammahi M, Arora DK, Moran AW, Proudman CJ, Ninomiya Y, Shirazi-Beechey SP.The heteromeric sweet taste receptor T1R2-T1R3 is expressed on the luminal membrane of certain populations of enteroendocrine cells. Sensing of sugars and other sweet compounds by this receptor activates a pathway in enteroendocrine cells, resulting in secretion of a number of gut hormones, including glucagon-like peptide 2 (GLP-2). This subsequently leads to upregulation in the expression of intestinal Na(+)/glucose cotransporter, SGLT1, and increased intestinal glucose absorption. On the basis of the current information available on the horse genome sequence, it has been proposed that the ge...
Goodrich LR, Chen AC, Werpy NM, Williams AA, Kisiday JD, Su AW, Cory E, Morley PS, McIlwraith CW, Sah RL, Chu CR.The chondrogenic potential of culture-expanded bone-marrow-derived mesenchymal stem cells (BMDMSCs) is well described. Numerous studies have also shown enhanced repair when BMDMSCs, scaffolds, and growth factors are placed into chondral defects. Platelets provide a rich milieu of growth factors and, along with fibrin, are readily available for clinical use. The objective of this study was to determine if the addition of BMDMSCs to an autologous platelet-enriched fibrin (APEF) scaffold enhances chondral repair compared with APEF alone. Methods: A 15-mm-diameter full-thickness chondral defect wa...
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...
Smith RK, Garvican ER, Fortier LA.The horse is an attractive model for many human age-related degenerative diseases of the musculoskeletal system because it is a large animal species that both ages and exercises, and develops naturally occurring injuries with many similarities to the human counterpart. It therefore represents an ideal species to use as a 'proving ground' for new therapies, most notably regenerative medicine. Regenerative techniques using cell-based therapies for the treatment of equine musculoskeletal disease have been in use for over a decade. This review article provides a summary overview of the sources, cu...
Bureau F, Delhalle S, Bonizzi G, Fiévez L, Dogné S, Kirschvink N, Vanderplasschen A, Merville MP, Bours V, Lekeux P.In most cells trans-activating NF-kappaB induces many inflammatory proteins as well as its own inhibitor, IkappaB-alpha, thus assuring a transient response upon stimulation. However, NF-kappaB-dependent inflammatory gene expression is persistent in asthmatic bronchi, even after allergen eviction. In the present report we used bronchial brushing samples (BBSs) from heaves-affected horses (a spontaneous model of asthma) to elucidate the mechanisms by which NF-kappaB activity is maintained in asthmatic airways. NF-kappaB activity was high in granulocytic and nongranulocytic BBS cells. However, NF...
Mazerbourg S, Overgaard MT, Oxvig C, Christiansen M, Conover CA, Laurendeau I, Vidaud M, Tosser-Klopp G, Zapf J, Monget P.IGF binding protein-4 (IGFBP-4) proteolytic degradation is a common feature of preovulatory follicles from human, ovine, bovine, porcine, and equine ovary. In all these species, the protease is a zinc-dependent metalloprotease and its ability to degrade IGFBP-4 is IGF dependent. The human intrafollicular IGFBP-4-degrading protease has recently been identified as pregnancy-associated plasma protein-A (PAPP-A). The aim of this study was to investigate whether PAPP-A is also involved in IGFBP-4 degradation in ovine, bovine, porcine, and equine preovulatory follicles and to study the expression of...
Arregui L, Rathi R, Zeng W, Honaramooz A, Gomendio M, Roldan ER, Dobrinski I.Xenografting of testis tissue from immature males from several mammalian species to immunodeficient mouse hosts results in production of fertilization-competent sperm. However, the efficiency of testis tissue xenografting from adult donors has not been critically evaluated. Testis tissue xenografting from sexually mature animals could provide an option to preserve the genetic material from valuable males when semen for cryopreservation cannot be collected. To assess the potential use of this technique for adult individuals, testes from adult animals of six species (pig, goat, cattle, donkey, h...
Goodrich LR, Choi VW, Carbone BA, McIlwraith CW, Samulski RJ.Cell transplantation for the treatment of joint disease is an important clinical tool. Genetic modification of cells before transplantation has shown enhanced healing. Ex vivo genetic modification of joint tissue cells with various adeno-associated virus (AAV) serotypes has not been investigated. The transduction efficiencies of self-complementary AAV serotypes (1-6 and 8) were determined in joint tissue containing chondrocytes and synoviocytes isolated from equine models. When comparing scAAV serotypes for efficient transduction ex vivo, in chondrocytes versus synoviocytes, serotypes 6 and 2,...
Baskurt OK, Farley RA, Meiselman HJ.Horse blood has a higher tendency to form red blood cell (RBC) aggregates compared with human blood, with this enhanced aggregation previously attributed to differences in plasma factors. Our results confirm this observation and further indicate that washed horse RBC also have a significantly higher aggregation tendency in dextran 70 solutions (i.e., horse RBC have a higher "aggregability"). In contrast, the aggregation tendency of rat RBC, both in autologous plasma and in dextran 70, is significantly less compared with human and horse RBC. Other rheological findings for horse and rat RBC incl...
Nichols AEC, Settlage RE, Werre SR, Dahlgren LA.Tendinopathies are common and difficult to resolve due to the formation of scar tissue that reduces the mechanical integrity of the tissue, leading to frequent reinjury. Tenocytes respond to both excessive loading and unloading by producing pro-inflammatory mediators, suggesting that these cells are actively involved in the development of tendon degeneration. The transcription factor scleraxis (Scx) is required for the development of force-transmitting tendon during development and for mechanically stimulated tenogenesis of stem cells, but its function in adult tenocytes is less well-defined. ...
Barrachina L, Cequier A, Romero A, Vitoria A, Zaragoza P, Vázquez FJ, Rodellar C.Antibody production after allogeneic administration of mesenchymal stem cells (MSCs) could impact their clinical application. Proinflammatory priming of MSCs can potentiate their regulatory ability in vivo but increased expression of major histocompatibility complex (MHC) might augment their immunogenicity, potentially leading to immune memory thus limiting repeated allogeneic administration. This study aimed at evaluating the production of cytotoxic allo-antibodies directed against donor's ELA (equine leukocyte antigen) in mismatched and halfmatched horses receiving repeated intraarticular ad...
Muttini A, Valbonetti L, Abate M, Colosimo A, Curini V, Mauro A, Berardinelli P, Russo V, Cocciolone D, Marchisio M, Mattioli M, Tosi U....In vitro expanded and frosted ovine amniotic epithelial cells (oAECs) were evaluated for their phenotype, stemness and attitude to differentiate into tenocytes. Fifteen horses with acute tendon lesions were treated with one intralesional injection of oAECs. Tendon recovery under controlled training was monitored. In vitro expanded oAECs showed a constant proliferative ability, a conserved phenotype and stable expression profile of stemness markers. Differentiation into tenocytes was also regularly documented. US controls showed the infilling of the defect and early good alignment of the fibers...
Bedford-Guaus SJ, McPartlin LA, Xie J, Westmiller SL, Buffone MG, Roberson MS.Oocyte activation at fertilization is brought about by the testis-specific phospholipase C zeta (PLCZ), owing to its ability to induce oscillations in intracellular Ca(2+) concentration ([Ca(2+)](i)). Whereas this is a highly conserved mechanism among mammals, important species-specific differences in PLCZ sequence, activity, and expression have been reported. Thus, the objectives of this research were to clone and characterize the intracellular Ca(2+)-releasing activity and expression of equine PLCZ in sperm and testis. Molecular cloning of equine PLCZ yielded a 1914-bp sequence that translat...
Christoffersen M, Troedsson M.A transient uterine inflammation post-breeding is a normal physiological reaction in the mare, and it is believed that the inflammatory response is necessary to eliminate bacteria and excess spermatozoa introduced into the uterine lumen. A tight balance between multiple pro- and anti-inflammatory factors is required for resolving the breeding-induced inflammation within 24-36 hr in the reproductively healthy mare, whereas a subpopulation of mares is susceptible to development of a persistent infection that can interfere with fertility. The aetiology of persistent endometritis can be either ba...
Kitamoto N, Ramig RF, Matson DO, Estes MK.The production of viral antigen after infection of MA104, HepG2 (derived from human liver), and CaCo-2 (derived from human colon) cells with various cultivatable human and animal rotavirus strains was compared using immunofluorescence tests. All rotavirus strains examined expressed antigen in CaCo-2 cells and MA104 cells, but only some virus strains, namely, SA11-Cl3 (simian), RRV (simian), CU-1 (canine), and Ty1 (turkey), produced antigen in numbers of infected HepG2 cells comparable to infections in MA104 and CaCo-2 cells. Fl-14 (equine), OSU (porcine), NCDV (bovine), and Ch2 (chicken) strai...
Frisbie DD, McCarthy HE, Archer CW, Barrett MF, McIlwraith CW.We sought to determine the effectiveness of chondroprogenitor cells derived from autologous and allogenic articular cartilage for the repair of cartilage defects in an equine model. Methods: Cartilage defects (15 mm) were created on the medial trochlear ridge of the femur. The following experimental treatments were compared with empty-defect controls: fibrin only, autologous chondroprogenitor cells plus fibrin, and allogenic chondroprogenitor cells plus fibrin (n = 4 or 12 per treatment). Horses underwent strenuous exercise throughout the twelve-month study, and evaluations included lameness (...
Kinaci A, Bergmann W, Bleys RL, van der Zwan A, van Doormaal TP.The biocompatibility, biodegradation, feasibility, and efficacy of medical devices like dural sealants and substitutes are often evaluated in various animal models. However, none of these studies explain the rationale for choosing a particular species, and a systematic interspecies comparison of the dura is not available. We hypothesized that histologic characteristics of the dura would differ among species. We systematically investigated basic characteristics of the dura, including thickness, composition, and fibroblast orientation of the dura mater, in 34 samples representing 10 animal speci...
Frampton AR, Uchida H, von Einem J, Goins WF, Grandi P, Cohen JB, Osterrieder N, Glorioso JC.To initiate infection, equine herpesvirus type 1 (EHV-1) attaches to heparan sulfate on cell surfaces and then interacts with a putative glycoprotein D receptor(s). After attachment, virus entry occurs either by direct fusion of the virus envelope with the plasma membrane or via endocytosis followed by fusion between the virus envelope and an endosomal membrane. Upon fusion, de-enveloped virus particles are deposited into the cytoplasm and travel to the nucleus for viral replication. In this report, we examined the mechanism of EHV-1 intracellular trafficking and investigated the ability of EH...
Kasashima Y, Ueno T, Tomita A, Goodship AE, Smith RK.Mesenchymal stem cell (MSC) therapy for orthopaedic disease is being used with increasing frequency; there is a need to define a safe, reliable and effective technique for the recovery of MSCs from the sternum of the horse. Objective: To describe an optimised safe technique for obtaining bone marrow-derived MSCs from the sternum of the Thoroughbred horse. Methods: The anatomical relationship of the sternum with the heart and internal anatomy was demonstrated in cadavers. Sternal anatomy was evaluated ultrasonographically and after midline sectioning. Sternebrae were examined histologically aft...
Menarim BC, Gillis KH, Oliver A, Ngo Y, Werre SR, Barrett SH, Rodgerson DH, Dahlgren LA.Synovitis is a major component of osteoarthritis and is driven primarily by macrophages. Synovial macrophages are crucial for joint homeostasis (M2-like phenotype), but induce inflammation (M1-like) when regulatory functions become overwhelmed. Macrophage phenotypes in synovium from osteoarthritic and healthy joints are poorly characterized; however, comparative knowledge of their phenotypes during health and disease is paramount for developing targeted treatments. This study compared patterns of macrophage activation in healthy and osteoarthritic equine synovium and correlated histology with ...
Giovannini S, Brehm W, Mainil-Varlet P, Nesic D.Tissue engineering (TE) has emerged as a promising new therapy for the treatment of damaged tissues and organs. Adult stem cells are considered as an attractive candidate cell type for cell-based TE. Mesenchymal stem cells (MSC) have been isolated from a variety of tissues and tested for differentiation into different cell lineages. While clinical trials still await the use of human MSC, horse tendon injuries are already being treated with autologous bone marrow-derived MSC. Given that the bone marrow is not an optimal source for MSC due to the painful and risk-containing sampling procedure, i...
