Characterization of the single cell landscape in normal and osteoarthritic equine joints.

Background: Osteoarthritis (OA) is a major source of pain and disability worldwide. Understanding of disease progression is evolving, but OA is increasingly thought to be a multifactorial disease in which the innate immune system plays a role in regulating and perpetuating low-grade inflammation. The aim of this study was to enhance our understanding of OA immunopathogenesis through characterization of the transcriptomic responses in OA joints, with the goal to facilitate the development of targeted therapies.

Review of skin grafting in equine wounds: indications and techniques.

Skin grafting is a simple technique that can be performed by equine practitioners to improve cosmetic outcomes in wounds with large skin defects that would not heal functionally or cosmetically with standard wound therapy interventions. Successful skin grafting is not difficult but relies upon appropriate preparation of the wound bed and effective immobilisation of the grafted area after skin graft placement. Prior to grafting, the wound bed should be treated with a moist wound healing dressing to prepare the granulation tissue bed to receive the graft.

The potential for senotherapy as a novel approach to extend life quality in veterinary medicine.

Cellular senescence, a condition where cells undergo arrest and can assume an inflammatory phenotype, has been associated with initiation and perpetuation of inflammation driving multiple disease processes in rodent models and humans. Senescent cells secrete inflammatory cytokines, proteins, and matrix metalloproteinases, termed the senescence associated secretory phenotype (SASP), which accelerates the aging processes. In preclinical models, drug interventions termed "senotherapeutics" selectively clear senescent cells and represent a promising strategy to prevent or treat multiple age-related conditions in humans and veterinary species.

Evaluation of stem-cell therapies in companion animal disease models: a concise review (2015-2023).

Companion animals in veterinary medicine develop multiple naturally occurring diseases analogous to human conditions. We previously reported a comprehensive review on the feasibility, safety, and biologic activity of using novel stem cell therapies to treat a variety of inflammatory conditions in dogs and cats (2008-2015) [Hoffman AM, Dow SW. Concise review: stem cell trials using companion animal disease models.

Targeted transcriptomic analysis of synovial tissues from horses with septic arthritis treated with immune-activated mesenchymal stromal cells reveals induction of T-cell response pathways.

Objective: To investigate mechanistically the reported beneficial effects of immune-activated mesenchymal stromal cell (MSC) therapy to treat equine septic arthritis, leveraging Nanostring technology.

Animals: 8 Quarter Horses with induced tibiotarsal Staphylococcus aureus septic arthritis treated IA with either Toll-like receptor-3 agonist polyinosinic:polycytidylic acid-activated MSCs + vancomycin antimicrobials (TLR-MSC-VAN; n = 4) or antimicrobials (VAN; 4).

Methods: Synovial tissues were collected and fixed in neutral-buffered 10% formalin, and formalin-fixed paraffin-embedded synovial and osteochondral tissues were sequenced using a custom-designed 200-gene equine Nanostring nCounter immune panel to directly quantify expression of key immune and cartilage-related genes.

Preliminary evaluation of safety and migration of immune activated mesenchymal stromal cells administered by subconjunctival injection for equine recurrent uveitis.

Introduction: Equine recurrent uveitis (ERU), an immune mediated disease characterized by repeated episodes of intra-ocular inflammation, affects 25% of horses in the USA and is the most common cause of glaucoma, cataracts, and blindness. Mesenchymal stromal cells (MSCs) have immunomodulatory properties, which are upregulated by preconditioning with toll-like receptor agonists. The objective was to evaluate safety and migration of TLR-3 agonist polyinosinic, polycytidylic acid (pIC)-activated MSCs injected subconjunctivally in healthy horses prior to clinical application in horses with ERU.

Antimicrobial Properties of Equine Stromal Cells and Platelets and Future Directions.

Increasing antimicrobial resistance in veterinary practice has driven the investigation of novel therapeutic strategies including regenerative and biologic therapies to treat bacterial infection. Integration of biological approaches such as platelet lysate and mesenchymal stromal cell (MSC) therapy may represent adjunctive treatment strategies for bacterial infections that minimize systemic side effects and local tissue toxicity associated with traditional antibiotics and that are not subject to antibiotic resistance. In this review, we will discuss mechanisms by which biological therapies exert antimicrobial effects, as well as potential applications and challenges in clinical implementation in equine practice.

Erythrocyte removal from bone marrow aspirate concentrate improves efficacy as intra-articular cellular therapy in a rodent osteoarthritis model.

Background: Despite the high prevalence of osteoarthritis (OA), there remains a need for additional therapeutic options. Cellular therapies with minimally manipulated cells such as bone marrow aspirate concentrates (BMAC) are increasingly popular in the U.S.

Hoof Unevenness in Juvenile Quarter Horses During First 6 Months of Training.

The role of hoof morphology is increasingly recognized as a factor associated with lameness incidence in performance horses. The primary objective was to evaluate effect of training initiation on hoof unevenness in Quarter Horses (n = 42; 29 2-year-olds, 13 3-year-olds) over 6-months (m) in training (m0, m2, m4, and m6). Horses were objectively assessed for lameness (inertial sensor system) and photographs and radiographs of feet were taken.

Distinct differences in immunological properties of equine orthobiologics revealed by functional and transcriptomic analysis using an activated macrophage readout system.

Introduction: Multiple biological therapies for orthopedic injuries are marketed to veterinarians, despite a lack of rigorous comparative biological activity data to guide informed decisions in selecting a most effective compound. Therefore, the goal of this study was to use relevant bioassay systems to directly compare the anti-inflammatory and immunomodulatory activity of three commonly used orthobiological therapies (OTs): mesenchymal stromal cells (MSC), autologous conditioned serum (ACS), and platelet rich plasma (PRP).

Methods: Equine monocyte-derived macrophages were used as the readout system to compare therapies, including cytokine production and transcriptomic responses.

Successful surgical removal of a pheochromocytoma in a mare via trans-costal approach.

Background: Pheochromocytomas have been previously reported in horses, but successful antemortem diagnosis and surgical removal without recurrence of clinical signs have not been described.

Objective: To report the clinical presentation, diagnostic evaluation, surgical technique, anaesthetic management and post-operative care of a mare diagnosed with pheochromocytoma.

Study Design: Clinical case report.

Effect of age at training initiation on hoof morphology and lameness in juvenile American Quarter Horses.

Background: Lameness, discipline, training intensity, environmental variability, and shoeing are all factors demonstrated to affect hoof loading and therefore act as adaptive stimuli to alter hoof morphology.

Objectives: To evaluate the effect of age at training initiation on hoof morphology and lameness incidence and determine if specific hoof morphology measurements correlate with lameness in juvenile American Quarter Horses.

Study Design: Prospective cohort study.

Liposomal bupivacaine is both safe and effective when administered via local infiltration at surgical site and mesovarium for laparoscopic ovariectomy in mares.

Background: Liposomal local anaesthetic solutions may provide extended-duration analgesia postoperatively but have not been assessed following intra-peritoneal local infiltration in any species.

Objectives: To evaluate two doses of 1.33% liposomal bupivacaine (LB) versus 0.

TLR-activated mesenchymal stromal cell therapy and antibiotics to treat multi-drug resistant septic arthritis in an equine model.

Background: 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 rodent biofilm infection models and dogs with spontaneous multi-drug-resistant infections.

Novel ocular immunotherapy induces tumor regression in an equine model of ocular surface squamous neoplasia.

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.

Immune Activated Cellular Therapy for Drug Resistant Infections: Rationale, Mechanisms, and Implications for Veterinary Medicine.

Antimicrobial resistance and biofilm formation both present challenges to treatment of bacterial infections with conventional antibiotic therapy and serve as the impetus for development of improved therapeutic approaches. Mesenchymal stromal cell (MSC) therapy exerts an antimicrobial effect as demonstrated in multiple acute bacterial infection models. This effect can be enhanced by pre-conditioning the MSC with Toll or Nod-like receptor stimulation, termed activated cellular therapy (ACT).

Intravenous injection of adipose-derived mesenchymal stromal cells benefits gait and inflammation in a spontaneous osteoarthritis model.

Osteoarthritis (OA) is a leading cause of morbidity among aging populations, yet symptom and/or disease-modification remains elusive. Adipose-derived mesenchymal stromal cells (adMSCs) have demonstrated immunomodulatory and anti-inflammatory properties that may alleviate clinical signs and interrupt disease onset and progression. Indeed, multiple manuscripts have evaluated intra-articular administration of adMSCs as a therapeutic; however, comparatively few evaluations of systemic delivery methods have been published.

Evaluation of factors associated with surgical site infection in equine proximal interphalangeal joint arthrodesis: 54 cases (2010-2019).

Background: The frequency of surgical site infection (SSI) following orthopaedic implant placement in horses has been reported but not compared with respect to specific antibiotic protocols administered.

Objectives: To determine factors associated with SSI in horses undergoing proximal interphalangeal joint (PIPJ) arthrodesis including perioperative antibiotic protocols.

Methods: Records were evaluated (2010-2019), and horses undergoing PIPJ arthrodesis were identified.

Liposomal bupivacaine provides longer duration analgesia than bupivacaine hydrochloride in an adjustable sole-pressure model of equine lameness.

Objective: To compare the efficacy and duration of action for perineural analgesia with liposomal bupivacaine (LB) versus bupivacaine hydrochloride (BHCl) in a sole-pressure induced model of forelimb lameness in horses.

Animals: 6 healthy adult research horses.

Procedures: In 1 randomly assigned forelimb, grade 3/5 lameness was induced by use of a sole-pressure lameness model.

Intra-articular administration of antibiotics in horses: Justifications, risks, reconsideration of use and outcomes.

Antibiotics have been injected intra-articularly by equine veterinarians for decades, either prophylactically when other drugs are administered for osteoarthritis or therapeutically to treat septic arthritis. This route of administration has also more recently gained attention in human orthopaedic clinical practice, particularly as an alternative to systemic antibiotic administration to treat infections following prosthetic arthroplasty. While the rationale for injecting antibiotics intra-articularly has been largely focused on achieving high local drug concentrations, there has been relatively little focus on pharmacokinetic parameters of antibiotics administered by this route, or on the potential for local toxicity.

Outcomes following single, caudally based bilateral versus unilateral frontonasal sinusotomy for treatment of equine paranasal sinus disease.

Background: Bilateral sinus disease is relatively uncommon in horses, accounting for 3%-4.5% of horses with sinonasal disease, but may require bilateral paranasal surgery for complete resolution. Complications and recurrence following bilateral sinusotomy have not been reported or compared to those following unilateral procedures.

Comparison of equine synovial sepsis rate following intrasynovial injection in ambulatory versus hospital settings.

Background: Frequency of synovial sepsis in horses following intrasynovial injection has been reported, but not compared with respect to the environment in which the injection was performed.

Objectives: To describe occurrence of synovial sepsis following intrasynovial injections performed in ambulatory vs hospital settings.

Study Design: Retrospective cohort study.

Outcomes after cervical vertebral interbody fusion using an interbody fusion device and polyaxial pedicle screw and rod construct in 10 horses (2015-2019).

Background: Further development of surgical techniques for equine cervical stabilisation is necessary to make the procedure less technically demanding, reduce complications and improve outcomes.

Objective: To describe clinical outcomes and owner reports in horses undergoing placement of an interbody fusion device and polyaxial pedicle screw and rod construct for cervical vertebral fusion in horses with cervical vertebral compressive myelopathy.

Study Design: Retrospective case series.

Toll-like receptor activation of equine mesenchymal stromal cells to enhance antibacterial activity and immunomodulatory cytokine secretion.

Objective: 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.

Study Design: Controlled laboratory study.

Sample Population: Equine bone-marrow-derived MSCs (three horses).

Susceptibility of canine chondrocytes and synoviocytes to antibiotic cytotoxicity in vitro.

Objective: To evaluate relative cytotoxicity of antibiotics to normal canine joint tissues in vitro.

Study Design: Experimental in vitro study.

Sample Population: Chondrocytes and synoviocytes (three dogs); cartilage explants (three dogs); six dogs total.