Immunomodulatory agents are substances that can modify or regulate one or more immune functions in horses. These agents can either enhance or suppress the immune response, depending on the desired outcome. In equine medicine, immunomodulatory therapies may be employed to manage various conditions, including autoimmune disorders, allergies, and infections. This topic encompasses research on the mechanisms of action, therapeutic applications, and effects of different immunomodulatory agents in horses. The page aggregates peer-reviewed studies and scholarly articles that investigate the efficacy, safety, and clinical implications of using immunomodulatory treatments in equine health management.
Terpeluk ER, Schäfer J, Finkler-Schade C, Schuberth HJ.Feed supplements supporting animal welfare and performance are becoming increasingly important. Immunomodulatory effects of such products have been observed in many species. The aim of this study was to analyze whether food supplementation with a fermentation product (SCFP) affects the occurrence of foal diarrhea in early life, and whether the SCFP feeding has an impact on the immediate response to a parenteral vaccination at the age of 6-9 months. Eleven foals received the SCFP (OLI) and eleven foals were fed a placebo (PLA) for 29 days. Growth, diarrhea, and diarrhea severity were observed ...
Carlier S, Depuydt E, Van Hecke L, Martens A, Saunders J, Spaas JH.Mesenchymal stem cells provide a valuable treatment option in orthopedic injuries in horses. Unassigned: The aim of this study was to evaluate the hematological, biochemical, immunological and immunomodulatory parameters following intralesional treatment with tenogenic primed equine allogeneic peripheral blood-derived mesenchymal stem cells (tpMSCs) in client-owned horses with naturally occurring superficial digital flexor tendon (SDFT) and suspensory ligament (SL) injuries. Unassigned: The immunogenicity and immunomodulatory capacities of tpMSCs were assessed in a modified mixed lymphocyte re...
Bello K, Lorch G, Papich MG, Kim K, Toribio RE, Yan L, Xie Z, Hill K, Phelps MA.Additional immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunomodulatory agent used in human and veterinary medicine for the prevention of graft rejection and the management of autoimmune diseases. Few studies exist investigating the pharmacokinetics of MMF in horses. The aim of this study was to evaluate the pharmacokinetics of a single dose of MMF in healthy horses in the fed vs. fasted state. Six healthy Standardbred mares were administered MMF 10 mg/kg by a nasogastric (NG) tube in a fed and fasted state. ...
Leal Reis I, Lopes B, Sousa P, Sousa AC, Branquinho MV, Caseiro AR, Rêma A, Briote I, Mendonça CM, Santos JM, Atayde LM, Alvites RD, Maurício AC.Horses are high-performance athletes prone to sportive injuries such as tendonitis and desmitis. The formation of fibrous tissue in tendon repair remains a challenge to overcome. This impels regenerative medicine to develop innovative therapies that enhance regeneration, retrieving original tissue properties. Multipotent Mesenchymal Stem/Stromal Cells (MSCs) have been successfully used to develop therapeutic products, as they secrete a variety of bioactive molecules that play a pivotal role in tissue regeneration. These factors are released in culture media for producing a conditioned medium (...
Berghaus LJ, Cathcart J, Berghaus RD, Ryan C, Toribio RE, Hart KA.Rhodococcus equi (R. equi), a pneumonia-causing intracellular bacterium, results in significant morbidity and mortality in young foals, while healthy adult horses rarely develop disease. Survival and replication within alveolar macrophages (AMφ) are the hallmarks of R. equi's pathogenicity. The vitamin D receptor (VDR) and its ligand, the active vitamin D metabolite 1,25(OH)2D, are important in immune responses to intracellular bacteria. The vitamin D/VDR pathway regulates the downstream production of cytokines in infected human AMφ. The immunomodulatory role of the vitamin D/VDR pathway in ...
Cooper HE, Bowlby C, Long S, Durgam SS.To investigate matrix metalloproteinase (MMP) and their inhibitors tissue inhibitor matrix metalloproteinase (TIMP) gene expression and secretion during equine deep digital flexor tendon (DDFT) tenocyte and macrophage (undifferentiated, proinflammatory, and regulatory) co-culture. Methods: Third passage DDF tenocytes and donor-matched macrophages differentiated from peripheral blood CD14+ monocytes from 5 healthy horses ages 9-11 years, euthanized for reasons unrelated to musculoskeletal conditions. Methods: Passage 3 DDT tenocyte aggregate cultures were co-cultured with undifferentiated (cont...
Koch DW, Schnabel LV.Tendon injuries are common in both veterinary and human clinical patients and result in morbidity, pain, and lost athletic performance. Consequently, utilizing naturally occurring injuries in veterinary patients as a comparative model could inform the development of novel therapies and increase translation for the treatment of human tendon injuries. Mesenchymal stem cells (MSCs) have shown considerable efficacy for the treatment of experimental and clinical superficial digital flexor tendon injury in the horse; however, the reinjury rate following treatment can remain high and MSC efficacy in ...
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...
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...
Saba C, Eggleston R, Parks A, Peroni J, Sjoberg E, Rice S, Tyma J, Williams J, Grosenbaugh D, Leard AT.Sarcoid tumors are common in horses and may negatively impact the performance and value of the horse. No known treatment is reliably successful. Objective: To determine tolerability, overall response rate, time to response, and progression-free survival of horses with biopsy-confirmed or suspected sarcoids treated with ALVAC-fIL2. Methods: Client-owned horses with measurable, presumed- or biopsy-confirmed sarcoid tumors. Methods: Prospective pilot study. One milliliter of ALVAC-fIL2 was injected into 4 to 5 areas of the sarcoid(s) in each horse (week 0); this treatment was repeated in weeks 1,...
Mund SJK, MacPhee DJ, Campbell J, Honaramooz A, Wobeser B, Barber SM.Limb wounds are common in horses and often develop complications. Intravenous multipotent mesenchymal stromal cell (MSC) therapy is promising but has risks associated with intravenous administration and unknown potential to improve cutaneous wound healing. The objectives were to determine the clinical safety of administering large numbers of allogeneic cord blood-derived MSCs intravenously, and if therapy causes clinically adverse reactions, accelerates wound closure, improves histologic healing, and alters mRNA expression of common wound cytokines. Wounds were created on the metacarpus of 12 ...
Lucassen A, Finkler-Schade C, Schuberth HJ. () fermentation products (SCFP) are used in animal husbandry as pre- and postbiotic feed supplements. A variety of immunomodulatory effects are noted in many species. The purpose of this study was to test the hypothesis that horses fed with SCFP containing feed additive Olimond BB display a modulated early immune response after influenza vaccination. Six horses received Olimond BB pellets (OLI) and five horses were fed placebo pellets (PLA) for 56 days. On day 40 all horses were vaccinated with a recombinant influenza A/equi-2 vaccine. At the day of vaccination, the groups did not differ in t...
Zayed M, Adair S, Dhar M.Synovial fluid contains cytokines, growth factors and resident mesenchymal stem cells (MSCs). The present study aimed to (1) determine the effects of autologous and allogeneic synovial fluid on viability, proliferation and chondrogenesis of equine bone marrow MSCs (BMMSCs) and (2) compare the immunomodulatory properties of equine synovial fluid MSCs (SFMSCs) and BMMSCs after stimulation with interferon gamma (INF-γ). To meet the first aim of the study, the proliferation and viability of MSCs were evaluated by MTS and calcein AM staining assays. To induce chondrogenesis, MSCs were cultured in ...
Cameron AD, Even KM, Linardi RL, Berglund AK, Schnabel LV, Engiles JB, Ortved KF.Joint injury can cause posttraumatic inflammation, which if severe enough can lead to posttraumatic osteoarthritis (PTOA), a progressive and debilitating condition. Posttraumatic inflammation is characterized by an influx of T lymphocytes and upregulation of inflammatory cytokines and degradative enzymes by activated chondrocytes and synoviocytes. Intra-articular bone marrow-derived mesenchymal stem cell (BM-MSC) injection for the treatment of osteoarthritis (OA) has been of interest due to the immunomodulatory properties of these cells. Interleukin (IL)-10, a potent immunomodulatory cytokine,...
Pezzanite L, Chow L, Griffenhagen G, Dow S, Goodrich L.Culture and expansion of equine mesenchymal stromal cells (MSCs) are routinely performed using fetal bovine serum (FBS) as a source of growth factors, nutrients, and extracellular matrix proteins. However, the desire to minimize introduction of xenogeneic bovine proteins or pathogens and to standardize cellular products intended for clinical application has driven evaluation of alternatives to FBS. Replacement of FBS in culture for several days before administration has been proposed to reduce antigenicity and potentially prolong survival after injection. However, the functional consequences o...
Pezzanite LM, Chow L, Johnson V, Griffenhagen GM, Goodrich L, Dow S.To evaluate effects of Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptor (TLR, NLR) ligand stimulation of equine mesenchymal stromal cells (MSCs) on antibacterial and immunomodulatory properties in vitro. Methods: Controlled laboratory study. Methods: Equine bone-marrow-derived MSCs (three horses). Methods: MSCs were stimulated with TLR (polyinosinic:polycytidylic acid [pIC] and lipopolysaccharide [LPS]) and NLR agonists (γ-d-Glu-mDAP [IE-DAP]) for 2 h, and plated at 1 × 105 cells/well 24 h. MSC-conditioned media (MSC-CM) were collected and assessed for antimicr...
Li J, Zhao Y, Gao Y, Zhu Y, Holyoak GR, Zeng S.Bacterial infections are the main causes of endometritis in mares. It is well known that the most common bacterial pathogen is Streptococcus equi subspecies zooepidemicus (SEZ). This structured review was completed according to the PRISMA procedure to search endometritis treatment protocols published between 1990 and 2020 it was our intent to evaluate the actual effects of different treatment protocols for endometritis caused by SEZ. The trials included were collected from Pubmed, CAB and Agricola. Ten articles with 116 horses and 17 different interventions were identified. The results of this...
Connard SS, Linardi RL, Even KM, Berglund AK, Schnabel LV, Ortved KF.The immunomodulatory properties of mesenchymal stem cells (MSCs) have been studied extensively due to their increasing clinical application for tissue regeneration and repair following culture expansion. We have studied the effect of continuous passage on the immunomodulatory capacity of equine bone marrow-derived MSCs (BM-MSCs). Equine BM-MSCs were isolated and culture expanded to passage three, six, and nine (P3, P6, P9). Immunomodulatory properties of each passage were assessed using a T cell proliferation assay and cytokine synthesis following stimulation with interferon gamma (IFN-γ). Re...
Berglund AK, Long JM, Robertson JB, Schnabel LV.Allogeneic mesenchymal stem cells (MSCs) are a promising cell therapy for treating numerous diseases, but major histocompatibility complex (MHC)-mismatched MSCs can be rejected by the recipient's immune system. Pre-treating MSCs with transforming growth factor-β2 (TGF-β2) to downregulate surface expression of MHC molecules may enhance the ability of allogeneic MSCs to evade immune responses. We used lymphocyte proliferation assays and ELISAs to analyze the immunomodulatory potential of TGF-β2-treated equine bone marrow-derived MSCs. T cell activation and cytotoxicity assays were then used t...
Bastos FZ, Barussi FCM, Leite LMB, Jamur VR, Soares AA, Senegaglia AC, Michelotto PV.This study aimed to assess the safety and reproducibility of cell therapy for its use in clinical practice. We performed immunophenotypic characterization of equine bone marrow-derived mesenchymal stromal cells (BMMSCs) by flow cytometry using CD90, CD19, CD14, CD105, CD45, and HLA-DR markers (n = 4); GTG banding cytogenetic analysis (n = 3); and microbiological quality control (n = 4). The immunomodulatory potentials of BMMSCs (n = 4) and its conditioned medium (CM, n = 3) were investigated by in vitro lymphocyte inhibition assay using phytohemagglutinin (PHA)-stimulated peripheral ...
Fedorka CE, Murase H, Loux SC, Loynachan AT, Walker OF, Squires EL, Ball BA, Troedsson MHT.Maintaining yearly foal production is important for the economic success of the broodmare, and this requires breeding to occur as quickly postpartum as possible. The initial postpartum estrus occurs within 5-20 days postpartum, whereas the uterus is still undergoing repair from tissue alterations during pregnancy and parturition, a process known as involution. Attempts have been made to hasten this process, but with minimal success. Mycobacterium cell wall fraction (MCWF) is an immunomodulator that has been shown to reduce bacterial growth and alter aspects of the immune response to breeding,...
Rostang A, Desjardins I, Espana B, Panzuti P, Berny P, Prouillac C, Pin D.This study aimed to investigate both the pharmacokinetic behavior and tolerance of methotrexate (MTX) in horses to design a specific dosing regimen as a new immunomodulatory drug for long-term treatment. To determine the primary plasma pharmacokinetic variables after single intravenous, subcutaneous or oral administration, six horses were administered 0.3 mg/kg MTX in a crossover design study. After a 10-week washout, MTX was administered subcutaneously to three of the six previously treated horses at a dose of 0.3 mg/kg once per week for 3 months. In both studies, MTX and metabolite concen...
MacDonald ES, Barrett JG.One hallmark of mesenchymal stem cells (MSCs) is the ability to differentiate into multiple tissue types which assists in tissue regeneration. Another hallmark of MSCs is their potent anti-inflammatory and immunomodulatory properties and the potential to treat inflammatory, immune-mediated, and ischemic conditions. In equine practice, MSCs have shown efficacy in the treatment of musculoskeletal disorders such as tendinopathy, meniscal tears and cartilage injury. However, there are many equine disease processes and conditions that may benefit from the immunomodulatory properties of MSCs. Exampl...
Yaneselli K, Barrachina L, Remacha AR, Algorta A, Vitoria A, Cequier A, Romero A, Vázquez FJ, Maisonnave J, Rodellar C.Propagation ex vivo of mesenchymal stem cells (MSCs) requires culture medium supplementation. Fetal bovine serum (FBS) has long been the gold standard supplement, but its use is being questioned mainly due to ethical and safety issues. The use of platelet lysate (PL) as substitute of FBS has been proposed but little is known about its effects on equine MSCs characteristics including their immune profile. The aim of this work was to investigate for the first time the effect of allogenic PL on the immunogenic and immunomodulatory gene expression profile of equine bone marrow derived MSCs (eBM-MS...
Mainguy-Seers S, Vargas A, Labrecque O, Bédard C, Hélie P, Lavoie JP.Neutrophilic inflammation is believed to contribute to the airway obstruction and remodelling in equine asthma. Azithromycin, an antibiotic with immunomodulatory properties, reduces pulmonary neutrophilia and hyper-responsiveness in human asthmatics and decreases airway remodelling in rodent models of asthma. It was therefore hypothesised that azithromycin would improve lung function, mucus accumulation and central airway remodelling by decreasing luminal neutrophilia in severe equine asthma. The effects of a 10-day treatment with either azithromycin or ceftiofur, an antimicrobial without immu...
MacKay RJ.All gray horses inherited a single gene mutation, STX17G, that unbalances melanocyte behavior to cause graying and propensities to develop vitiligo and melanoma. The coat color genes ASIPa and MC1RE add risk such that relative likelihood of melanoma based on pregraying coat color is black > bay > chestnut. Melanomas begin at about 4 years. Locoregional control of melanoma masses depends on surgical removal and/or intralesional chemotherapy (possibly with adjunctive hyperthermia or electroporation). Systemic treatment is not evidence based but immunomodulators (cimetidine, levamisole) and ...
Cassano JM, Schnabel LV, Goodale MB, Fortier LA.Inflammatory licensed mesenchymal stem cells (MSCs) have the ability to promote functional tissue repair. This study specifically sought to understand how the recipient tissue environment reciprocally affects MSC function. Inflammatory polarized macrophages, modeling an injured tissue environment, were exposed to licensed MSCs, and the resultant effects of MSC immunomodulation and functionality of the MSC secretome on chondrocyte homeostasis were studied. Inflammatory licensed MSCs were generated through priming with either IFN-γ or polyinosinic:polycytidylic acid (poly I:C). Macrophages were...
LeBlanc MM, Causey RC.Endometritis, a major cause of mare infertility arising from failure to remove bacteria, spermatozoa and inflammatory exudate post-breeding, is often undiagnosed. Defects in genital anatomy, myometrial contractions, lymphatic drainage, mucociliary clearance, cervical function, plus vascular degeneration and inflamm-ageing underlie susceptibility to endometritis. Diagnosis is made through detecting uterine fluid, vaginitis, vaginal discharge, short inter-oestrous intervals, inflammatory uterine cytology and positive uterine culture. However, these signs may be absent in subclinical cases. Hyper...
Barrachina L, Remacha AR, Romero A, Vázquez FJ, Albareda J, Prades M, Ranera B, Zaragoza P, Martín-Burriel I, Rodellar C.Mesenchymal stem cells (MSCs) are being investigated for the treatment of equine joint diseases because of their regenerative potential. Recently, the focus mainly has addressed to their immunomodulatory capacities. Inflammation plays a central role in joint pathologies, since the release of proinflammatory mediators to the synovial fluid (SF) leads to the activation of enzymatic degradation of the cartilage. MSCs can modulate the local immune environment through direct or paracrine interaction with immune cells, suppressing their proliferation and re-addressing their functions. Proinflammator...
Naskou MC, Sumner SM, Chocallo A, Kemelmakher H, Thoresen M, Copland I, Galipeau J, Peroni JF.Mesenchymal stem cells (MSCs) produced for clinical purposes rely on culture media containing fetal bovine serum (FBS) which is xenogeneic and has the potential to significantly alter the MSC phenotype, rendering these cells immunogenic. As a result of bovine-derived exogenous proteins expressed on the cell surface, MSCs may be recognized by the host immune system as non-self and be rejected. Platelet lysate (PL) may obviate some of these concerns and shows promising results in human medicine as a possible alternative to FBS. Our goal was to evaluate the use of equine platelet lysate (ePL) poo...
Cortés-Araya Y, Amilon K, Rink BE, Black G, Lisowski Z, Donadeu FX, Esteves CL.Equine mesenchymal stem/stromal cells (MSCs) are multipotent cells that are widely used for treatment of musculoskeletal injuries, and there is significant interest in expanding their application to nonorthopedic conditions. MSCs possess antibacterial and immunomodulatory properties that may be relevant for combating infection; however, comparative studies using MSCs from different origins have not been carried out in the horse, and this was the focus of this study. Our results showed that MSC-conditioned media attenuated the growth of Escherichia coli, and that this effect was, on average, mo...
Colbath AC, Dow SW, Phillips JN, McIlwraith CW, Goodrich LR.The use of allogeneic bone marrow-derived mesenchymal stem cells (BMDMSCs) may provide an effective alternative to autologous BMDMSCs for treatment of equine musculoskeletal injuries. However, concerns have been raised regarding the potential safety and effectiveness of allogeneic BMDMSCs. We conducted studies to assess the immunological properties of equine allogeneic BMDMSCs compared with those of autologous BMDMSCs. For assessment of inherent immunogenicity, the relative ability of allogeneic and autologous BMDMSCs to stimulate spontaneous proliferation of equine lymphocytes was compared. T...
Alicka M, Marycz K.Metabolic syndrome (MetS) is highly associated with a modern lifestyle. The prevalence of MetS has reached epidemic proportion and is still rising. The main cause of MetS and finally type 2 diabetes occurrence is excessive nutrient intake, lack of physical activity, and inflammatory cytokines secretion. These factors lead to redistribution of body fat and oxidative and endoplasmic reticulum (ER) stress occurrence, resulting in insulin resistance, increase adipocyte differentiation, and much elevated levels of proinflammatory cytokines. Cellular therapies, especially mesenchymal stem cell (MSC)...
De Schauwer C, Goossens K, Piepers S, Hoogewijs MK, Govaere JL, Smits K, Meyer E, Van Soom A, Van de Walle GR.Mesenchymal stromal cells (MSCs) have been extensively studied for their promising capabilities in regenerative medicine. Although bone marrow is the best-known source for isolating equine MSCs, non-invasive alternative sources such as umbilical cord blood (UCB), umbilical cord matrix (UCM), and peripheral blood (PB) have also been reported. Methods: Equine MSCs from three non-invasive alternative sources were isolated from six individual mares (PB) and their foals (UCB and UCM) at parturition. To minimize inter-horse variability, the samples from the three sources were matched within the same...
Ma G, Feineis S, Osterrieder N, Van de Walle GR.Major histocompatibility complex class I (MHC-I) molecules play an important role in host immunity to infection by presenting antigenic peptides to cytotoxic T lymphocytes (CTLs), which recognize and destroy virus-infected cells. Members of the Herpesviridae have developed multiple mechanisms to avoid CTL recognition by virtue of downregulation of MHC-I on the cell surface. We report here on an immunomodulatory protein involved in this process, pUL56, which is encoded by ORF1 of equine herpesvirus type 1 (EHV-1), an alphaherpesvirus. We show that EHV-1 pUL56 is a phosphorylated early protein w...
Pezzanite LM, Chow L, Johnson V, Griffenhagen GM, Goodrich L, Dow S.To evaluate effects of Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptor (TLR, NLR) ligand stimulation of equine mesenchymal stromal cells (MSCs) on antibacterial and immunomodulatory properties in vitro. Methods: Controlled laboratory study. Methods: Equine bone-marrow-derived MSCs (three horses). Methods: MSCs were stimulated with TLR (polyinosinic:polycytidylic acid [pIC] and lipopolysaccharide [LPS]) and NLR agonists (γ-d-Glu-mDAP [IE-DAP]) for 2 h, and plated at 1 × 105 cells/well 24 h. MSC-conditioned media (MSC-CM) were collected and assessed for antimicr...
MacDonald ES, Barrett JG.One hallmark of mesenchymal stem cells (MSCs) is the ability to differentiate into multiple tissue types which assists in tissue regeneration. Another hallmark of MSCs is their potent anti-inflammatory and immunomodulatory properties and the potential to treat inflammatory, immune-mediated, and ischemic conditions. In equine practice, MSCs have shown efficacy in the treatment of musculoskeletal disorders such as tendinopathy, meniscal tears and cartilage injury. However, there are many equine disease processes and conditions that may benefit from the immunomodulatory properties of MSCs. Exampl...
Fumuso EA, Aguilar J, Giguère S, Rivulgo M, Wade J, Rogan D.Our objective was to characterize immune parameters in susceptible (SM) and resistant (RM) mares, with and without artificial insemination (AI) and immunomodulation. Eight RM and eight SM were selected based on their reproductive history and functional tests. Both groups of mares were evaluated during three consecutive cycles: Cycle 1, untreated cycle (control); Cycle 2, AI with dead semen; Cycle 3, AI with dead semen and immunomodulation. Endometrial biopsies were taken during the three cycles as follows: Cycle 1--at estrus, when follicles > or =35mm and at diestrus (7+/-1 days after ovulatio...
Knottenbelt DC, Kelly DF.OBJECTIVE: Diagnosis and management of periorbital sarcoids in horses is a significant clinical challenge for the practicing veterinary surgeon and pathologist. The purpose of this study was to investigate the response of various types of sarcoids to different therapeutic methods. Animals studied Medical records of 445 clinical patients. Procedures This paper retrospectively examines the clinical and histological features of periorbital sarcoids and the treatment of 445 cases. Treatment by surgical excision, cryosurgery, Bacillus-Calmette-Gaérin (BCG) immunomodulation, topical cytotoxic appli...
Ceusters J, Lejeune JP, Sandersen C, Niesten A, Lagneaux L, Serteyn D.Bone marrow and adipose tissue represent the two most commonly exploited sources of adult mesenchymal stem cells for musculoskeletal applications. Unfortunately the sampling of bone marrow and fat tissue is invasive and does not always lead to a sufficient number of cells. The present study describes a novel sampling method based on microbiopsy of skeletal muscle in man, pigs, dogs and horses. The process includes explant of the sample, Percoll density gradient for isolation and subsequent culture of the cells. We further characterized the cells and identified their clonogenic and immunomodula...
Kim HY, Mott J, Zhi N, Tajima T, Rikihisa Y.Human granulocytic ehrlichiosis (HGE), a tick-borne zoonosis, is caused by an obligatory intragranulocytic bacterium, the HGE agent, a strain of Anaplasma phagocytophila. The equine model of HGE is considered valuable in understanding pathogenic and immune mechanisms of HGE. In the present study, cytokine mRNA expression by peripheral blood leukocytes (PBLs) in horses was examined during the course of infection by intravenous inoculation of A. phagocytophila or by allowing feeding by infected ticks. The p44 genes encoding the major outer membrane protein P44s of A. phagocytophila were detected...
Klier J, May A, Fuchs S, Schillinger U, Plank C, Winter G, Gehlen H, Coester C.Recurrent airway obstruction (RAO) in horses has become a common problem in stabled horses in industrialized countries and deserves new therapeutic strategies. CpG-oligodeoxynucleotides (CpG-ODNs) were developed as effective immunostimulating agents to induce a Th2/Th1 shift. These agents showed a beneficial therapeutic effect in allergic diseases with predominant Th2 immunoresponse. CpG-ODN delivery by gelatin nanoparticles (GNPs) resulted in enhanced cellular uptake in murine and human in vitro studies and was a starting point for the present trial. The aim of this study was to identify an o...
Ferris RA, Frisbie DD, McCue PM.Current treatments for Persistent mating-induced endometritis such as uterine lavage and oxytocin therapy focus on aiding the uterus in removal of inflammatory products, but these treatments do not modulate the inciting inflammatory response. Biological treatments, such as autologous conditioned serum (ACS) and mesenchymal stem cells (MSCs), have been used in human and veterinary medicine for immunomodulation for over 10 years. The objectives of this project were to evaluate the ability of ACS or MSCs to modulate the inflammatory response to spermatozoa after breeding. Two experiments were pe...
Klier J, Geis S, Steuer J, Geh K, Reese S, Fuchs S, Mueller RS, Winter G, Gehlen H.New therapeutic strategies to modulate the immune response of human and equine allergic asthma are still under extensive investigation. Immunomodulating agents stimulating T-regulatory cells offer new treatment options beyond conventional symptomatic treatment or specific immunotherapy for human and equine allergic airway diseases, with the goal of a homoeostatic T-helper cell balance. The aim of this study was to evaluate the effects of a nebulized gelatin nanoparticle-CpG formulation (CpG-GNP) with and without specific allergens for the treatment of spontaneous allergic equine asthma as a mo...
Li J, Zhao Y, Gao Y, Zhu Y, Holyoak GR, Zeng S.Bacterial infections are the main causes of endometritis in mares. It is well known that the most common bacterial pathogen is Streptococcus equi subspecies zooepidemicus (SEZ). This structured review was completed according to the PRISMA procedure to search endometritis treatment protocols published between 1990 and 2020 it was our intent to evaluate the actual effects of different treatment protocols for endometritis caused by SEZ. The trials included were collected from Pubmed, CAB and Agricola. Ten articles with 116 horses and 17 different interventions were identified. The results of this...
Stitz L, Bilzer T, Richt JA, Rott R.Borna disease represents a unique model of a virus-induced immunological disease of the brain. Naturally occurring in horses and sheep, the mechanisms of pathogenesis have been studied in experimental animals, namely in the rat. Many investigations have revealed that the infection of the natural hosts principally follows the same pathogenic pathways as observed in rats, leading to a severe encephalomyelitis. This affliction of the central nervous system results in severe neurological disorders that again, are fully comparable in laboratory animals to those in the natural and the different expe...
Yaneselli K, Barrachina L, Remacha AR, Algorta A, Vitoria A, Cequier A, Romero A, Vázquez FJ, Maisonnave J, Rodellar C.Propagation ex vivo of mesenchymal stem cells (MSCs) requires culture medium supplementation. Fetal bovine serum (FBS) has long been the gold standard supplement, but its use is being questioned mainly due to ethical and safety issues. The use of platelet lysate (PL) as substitute of FBS has been proposed but little is known about its effects on equine MSCs characteristics including their immune profile. The aim of this work was to investigate for the first time the effect of allogenic PL on the immunogenic and immunomodulatory gene expression profile of equine bone marrow derived MSCs (eBM-MS...
LeBlanc MM.Ascending placentitis is a common cause of premature birth, abortion and delivery of compromised, ill foals. Recent experimental models have investigated diagnostic procedures and treatment strategies in an attempt to improve live foal rate. Diagnostics such as transrectal and transabdominal ultrasonography are used to evaluate foetal well-being and placental separation, while measurement of plasma progestins or oestrogen identifies a stressed or hypoxic foetus. Treatment is directed at stopping spread of infection, maintaining uterine quiescence and blocking production of pro-inflammatory cyt...
Cameron AD, Even KM, Linardi RL, Berglund AK, Schnabel LV, Engiles JB, Ortved KF.Joint injury can cause posttraumatic inflammation, which if severe enough can lead to posttraumatic osteoarthritis (PTOA), a progressive and debilitating condition. Posttraumatic inflammation is characterized by an influx of T lymphocytes and upregulation of inflammatory cytokines and degradative enzymes by activated chondrocytes and synoviocytes. Intra-articular bone marrow-derived mesenchymal stem cell (BM-MSC) injection for the treatment of osteoarthritis (OA) has been of interest due to the immunomodulatory properties of these cells. Interleukin (IL)-10, a potent immunomodulatory cytokine,...
Ziebell KL, Steinmann H, Kretzdorn D, Schlapp T, Failing K, Schmeer N.The efficacy of an immunomodulator, Baypamun N, was tested in 4-10-month-old horses which were exposed to stress by weaning, transport and commingling with yearlings from different breeders (crowding). Verum (n = 26) and placebo animals (n = 27) received three intramuscular injections of the investigational preparations (days 0, 2, 9) starting at the day of commingling in one stable. The incidence of acute respiratory disease was high during the first 4 weeks after commingling. Approximately 50% of all horses showed seroconversion due to field infection by EHV1 and EHV4 during the observation ...
Woodward EM, Christoffersen M, Campos J, Horohov DW, Scoggin KE, Squires E, Troedsson MH.The first objective of this study was to evaluate intrauterine nitric oxide (NO) and endometrial inducible NO synthase (iNOS) in mares susceptible or resistant to persistent breeding-induced endometritis (PBIE) within 24 h after breeding. Mares susceptible (n = 6) or resistant (n = 6) to PBIE were inseminated over five cycles, and uterine secretions and endometrial biopsies were collected before and 2, 6, 12 and 24 h after insemination. Uterine secretions were analysed for NO and biopsies were analyzed for iNOS expression. A second experiment evaluated the effect of treatment with dexame...
Zayed M, Adair S, Dhar M.Synovial fluid contains cytokines, growth factors and resident mesenchymal stem cells (MSCs). The present study aimed to (1) determine the effects of autologous and allogeneic synovial fluid on viability, proliferation and chondrogenesis of equine bone marrow MSCs (BMMSCs) and (2) compare the immunomodulatory properties of equine synovial fluid MSCs (SFMSCs) and BMMSCs after stimulation with interferon gamma (INF-γ). To meet the first aim of the study, the proliferation and viability of MSCs were evaluated by MTS and calcein AM staining assays. To induce chondrogenesis, MSCs were cultured in ...
Ons E, Van Brussel L, Lane S, King V, Cullinane A, Kenna R, Lyons P, Hammond TA, Salt J, Raue R.The efficacy of Zylexis®, an immunomodulator in horses based on inactivated Parapoxvirus ovis (iPPVO), was assessed using an equine herpesvirus type 1 (EHV-1) challenge model in the presence of a natural infection with Streptococcus equi equi (S. equi). Eleven horses were treated with iPPVO and twelve were kept as controls. Six horses were challenged with EHV-1 and commingled with the horses on study. Animals were dosed on Days -2, 0 (just before commingling) and Day 7. On Day 11 significantly less nasal discharge, enlarged lymph nodes, EHV-1 shedding and lower rectal temperatures were observ...
Lucassen A, Finkler-Schade C, Schuberth HJ. () fermentation products (SCFP) are used in animal husbandry as pre- and postbiotic feed supplements. A variety of immunomodulatory effects are noted in many species. The purpose of this study was to test the hypothesis that horses fed with SCFP containing feed additive Olimond BB display a modulated early immune response after influenza vaccination. Six horses received Olimond BB pellets (OLI) and five horses were fed placebo pellets (PLA) for 56 days. On day 40 all horses were vaccinated with a recombinant influenza A/equi-2 vaccine. At the day of vaccination, the groups did not differ in t...
Pezzanite L, Chow L, Griffenhagen G, Dow S, Goodrich L.Culture and expansion of equine mesenchymal stromal cells (MSCs) are routinely performed using fetal bovine serum (FBS) as a source of growth factors, nutrients, and extracellular matrix proteins. However, the desire to minimize introduction of xenogeneic bovine proteins or pathogens and to standardize cellular products intended for clinical application has driven evaluation of alternatives to FBS. Replacement of FBS in culture for several days before administration has been proposed to reduce antigenicity and potentially prolong survival after injection. However, the functional consequences o...
Mainguy-Seers S, Vargas A, Labrecque O, Bédard C, Hélie P, Lavoie JP.Neutrophilic inflammation is believed to contribute to the airway obstruction and remodelling in equine asthma. Azithromycin, an antibiotic with immunomodulatory properties, reduces pulmonary neutrophilia and hyper-responsiveness in human asthmatics and decreases airway remodelling in rodent models of asthma. It was therefore hypothesised that azithromycin would improve lung function, mucus accumulation and central airway remodelling by decreasing luminal neutrophilia in severe equine asthma. The effects of a 10-day treatment with either azithromycin or ceftiofur, an antimicrobial without immu...
