Explore the vast range of titles available.

As the search for an immune privileged allogeneic donor mesenchymal stem cell (MSC) line continues in equine medicine, the characterization of the cells between different sources becomes important. Our research seeks to more clearly define the MSC marker expression of different equine MSC donors. The bone marrow-derived MSCs from two equine breeds and different blood donor-types were compared over successive culture passages to determine the differential expression of important antigens. Eighteen Thoroughbreds and 18 Standardbreds, including 8 blood donor (erythrocyte Aa, Ca, and Qa antigen negative) horses, were evaluated. Bone marrow was taken from each horse for isolation and culture of MSCs. Samples from passages 2, 4, 6, and 8 were labelled and evaluated by flow cytometry. The cell surface expression of CD11a/18, CD44, CD90 and MHC class II antigens were assessed. Trilineage assays for differentiation into adipogenic, chondrogenic and osteogenic lines were performed to verify characterization of the cells as MSCs. There were significant differences in mesenchymal stem cell marker expression between breeds and blood antigen-type groups over time. Standardbred horses showed a significantly lower expression of MHC class II than did Thoroughbred horses at passages 2, 4 and 6. CD90 was significantly higher in universal blood donor Standardbreds as compared to non-blood donor Standardbreds over all time points. All MSC samples showed high expression of CD44 and low expression of CD11a/18. Universal blood donor- type Standardbred MSCs from passages 2-4 show the most ideal antigen expression pattern of the horses and passages that we characterized for use as a single treatment of donor bone marrow-derived MSCs. Further work is needed to determine the significance of this differential expression along with the effect of the expression of MHC I on equine bone marrow-derived MSCs.

The paracrine signaling, immunogenic properties and possible applications of mesenchymal stromal cells (MSCs) for cartilage tissue engineering and regenerative medicine therapies have been investigated through numerous in vitro, animal model and clinical studies. The emerging knowledge largely supports the concept of MSCs as signaling and modulatory cells, exerting their influence through trophic and immune mediation rather than as a cell replacement therapy. The virtues of allogeneic cells as a ready‐to‐use product with well‐defined characteristics of cell surface marker expression, proliferative ability, and differentiation capacity are well established. With clinical applications in mind, a greater focus on allogeneic cell sources is evident, and this review summarizes the latest published and upcoming clinical trials focused on cartilage regeneration adopting allogeneic and autologous cell sources. Moreover, we review the current understanding of immune modulatory mechanisms and the role of trophic factors in articular chondrocyte‐MSC interactions that offer feasible targets for evaluating MSC activity in vivo within the intra‐articular environment. Furthermore, bringing labeling and tracking techniques to the clinical setting, while inherently challenging, will be extremely informative as clinicians and researchers seek to bolster the case for the safety and efficacy of allogeneic MSCs. We therefore review multiple promising approaches for cell tracking and labeling, including both chimerism studies and imaging‐based techniques, that have been widely explored in vitro and in animal models. Understanding the distribution and persistence of transplanted MSCs is necessary to fully realize their potential in cartilage regeneration techniques and tissue engineering applications. We summarize the latest published and upcoming clinical trials focused on cartilage regeneration adopting allogeneic and autologous cell sources. Moreover, we review the current understanding of immune modulatory mechanisms and trophic factors regulating mesenchymal stromal cell (MSC) activity in vivo, as well as multiple approaches for cell tracking and labeling in vitro and in vivo. Understanding the distribution and persistence of MSCs is necessary to fully realize potential cartilage regeneration techniques and tissue engineering applications.

Interest in the cervical spine as a cause of pain or dysfunction is increasingly becoming the focus of many equine practitioners. Many affected horses are presented for poor performance, while others will present with dramatic, sometimes dangerous behavior. Understanding and distinguishing the different types of neck pain is a starting point to comprehending how the clinical presentations can vary so greatly. There are many steps needed to systematically evaluate the various tissues of the cervical spine to determine which components are contributing to cervical pain and dysfunction. Osseous structures, soft tissues and the central and the peripheral nervous system may all play a role in these various clinical presentations. After completing the clinical evaluation, several imaging modalities may be implemented to help determine the underlying pathologic processes. There are multiple treatment options available and each must be carefully chosen for an individual horse. Provided is a synopsis of the current knowledge as to different disease processes that can result in cervical pain and dysfunction, diagnostic approaches and treatment strategies. Improving the knowledge in these areas will ideally help to return horses to a state of well-being that can be maintained over time and through the rigors of their job or athletic endeavors.

Background Autologous conditioned serum (ACS) has been extensively used in the field of veterinary orthopaedics and sports medicine. Due to the autologous and blood-derived nature of this product, issues such as individual variability, need for storage at low temperatures and non-availability for immediate are frequently encountered for ACS use in the field. To address those issues, we proposed the evaluation of an off-the-shelf allogeneic freeze-dried version of conditioned serum in an in vitro model of osteoarthritis. In this study, we evaluated if origin (autologous and allogeneic) and preparation (frozen and freeze-dried) of conditioned serum could influence in its effect in an in vitro model. Results IL-1β stimulation in cartilage led to a significant increase in media GAG and decreased levels of GAG in cartilage explants at the termination of the experiment. No significant differences were noted in outcomes measured in the cartilage explants with respect to the main effects of treatment (frozen versus freeze-dried serum), autologous versus allogeneic preparations or based on serum concentration. Conclusions The study did not observe any substantial differences in the response of cartilage to allogeneic freeze-dried CS when compared to other independent parameters (autologous and frozen preparations). Further investigation using in vivo systems appears warranted.

BackgroundRehabilitation of horses using underwater treadmill therapy has been shown to improve joint range of motion, joint mobility, stride length and proprioceptive parameters with experimental studies. However, studies investigating the prognosis and return to function following rehabilitation are lacking.MethodsA retrospective study of Thoroughbred racehorses treated with arthroscopic surgery for osteochondral fragments of the metacarpophalangeal (MCP) or metatarsophalangeal (MTP) joints or carpal joints undergoing conventional rehabilitation or underwater treadmill assisted rehabilitation at the same facility were included. The objective of the current study was to investigate if underwater treadmill assisted rehabilitation following arthroscopy in the Thoroughbred racehorse was positively associated with returning to racing, time to return to racing and postoperative racing performance including Beyer Speed Figures.ResultsSurgery was performed on 165 horses on 174 surgical occasions; 70 (40.2 per cent) underwent underwater treadmill rehabilitation, with the remainder undergoing conventional rehabilitation. The time to return to racing was a median of 227 (IQR 185–281) days and 239 (IQR 205–303) days for underwater treadmill and conventional rehabilitation, respectively (P=0.16). Of the horses that raced presurgery, 83 per cent (58/70) of underwater treadmill rehabilitated horses and 61 per cent (63/104) of horses undergoing conventional rehabilitation returned to racing following surgery (P=0.02).ConclusionUnderwater treadmill rehabilitation is superior in returning a Thoroughbred racehorse to racing following arthroscopic surgery of the carpus and/or MCP/MTP joints.

Background Platelet-rich plasma (PRP) as well as other platelet-derived products have been used as a potential disease-modifying treatment for musculoskeletal diseases, such as osteoarthritis (OA). The restorative properties of such products rely mainly on the high concentrations of growth factors, demonstrating encouraging results experimentally and clinically. Yet, the autologous blood-derived nature of the PRP product lead to limitations that precludes it’s widespread use. The main limitations for PRP use are; product variability, the need for minimum laboratory settings in most cases, and the need for storage at low temperatures to preserve its properties. Based on these limitations, the objective of this study was to investigate an allogeneic off-the-shelf platelet lysate (PL) in cartilage exposed to interleukin 1β (IL-1β). For this purpose, blood and cartilage were harvested from eight skeletally mature and healthy horses. Blood was processed into PL aliquots and divided into three groups (Frozen, Freeze-dried and Filtered freeze-dried), used in autologous and allogeneic conditions and in three different concentrations (1.5, 3 and 6-fold). Different PL preparations were then applied in cartilage culture with interleukin-1 beta and cultured for 10 days. Cartilage and media samples were collected and analyzed for total GAG and 35 SO 4 -labeled GAG content. Results No significant differences between the controls and PL groups in cartilage and media were demonstrated. The effects of PL on cartilage matrix were concentration dependent and intermediate concentrations (3-fold) in PL showed increased 35 SO 4 -labelled GAG in cartilage. Conclusion In conclusion, the allogeneic freeze-dried PL presented equivalent effects compared to frozen autologous PL. Intermediate platelet concentration on average demonstrated improved results, demonstrating less GAG loss compared to other concentrations.

Background Mesenchymal stromal cells (MSCs) are believed to be hypoimmunogeneic with potential use for allogeneic administration. Methods Bone marrow was harvested from Connemara ( n  = 1), Standardbred ( n  = 6), and Thoroughbred ( n  = 3) horses. MSCs were grouped by their level of expression of major histocompatibility factor II (MHC II). MSCs were then sub-grouped by those MSCs derived from universal blood donor horses. MSCs were isolated and cultured using media containing fetal bovine serum until adequate numbers were acquired. The MSCs were cultured in xenogen-free media for 48 h prior to use and during all assays. Autologous and allogeneic MSCs were then directly co-cultured with responder leukocytes from the Connemara horse in varying concentrations of MSCs to leukocytes (1:1, 1:10, and 1:100). MSCs were also cultured with complement present and heat-inactivated complement to determine whether complement alone would decrease MSC viability. MSCs underwent haplotyping of their equine leukocyte antigen (ELA) to determine whether the MHC factors were matched or mismatched between the donor MSCs and the responder leukocytes. Results All allogeneic MSCs were found to be ELA mismatched with the responder leukocytes. MHC II-low and universal blood donor MSCs caused no peripheral blood mononuclear cell (PBMC) proliferation, no increase in B cells, and no activation of CD8 lymphocytes. Universal blood donor MSCs stimulated a significant increase in the number of T regulatory cells. Neutrophil interaction with MSCs showed that universal blood donor and MHC II-high allogeneic MSCs at the 6 h time point in co-culture caused greater neutrophil activation than the other co-culture groups. Complement-mediated cytotoxicity did not consistently cause MSC death in cultures with active complement as compared to those with inactivated complement. Gene expression assays revealed that the universal blood donor group and the MHC II-low MSCs were more metabolically active both in the anabolic and catabolic gene categories when cultured with allogeneic lymphocytes as compared to the other co-cultures. These upregulated genes included CD59, FGF-2, HGF, IDO, IL-10, IL-RA, IL-2, SOX2, TGF-β1, ADAMSTS-4, ADAMSTS-5, CCL2, CXCLB/IL-8, IFNγ, IL-1β, and TNFα. Conclusions MHC II-low MSCs are the most appropriate type of allogeneic MSC to prevent activation of the innate and cell-mediated component of the adaptive immune systems and have increased gene expression as compared to other allogeneic MSCs.

Osteoarthritis is a leading cause of lameness and joint disease in horses. A simple, economical, and accurate diagnostic test is required for routine screening for OA. This study aimed to evaluate infrared (IR)-based synovial fluid biomarker profiling to detect early changes associated with a traumatically induced model of equine carpal osteoarthritis (OA). Unilateral carpal OA was induced arthroscopically in 9 of 17 healthy thoroughbred fillies; the remainder served as Sham-operated controls. The median age of both groups was 2 years. Synovial fluid (SF) was obtained before surgical induction of OA (Day 0) and weekly until Day 63. IR absorbance spectra were acquired from dried SF films. Following spectral pre-processing, predictive models using random forests were used to differentiate OA, Sham, and Control samples. The accuracy for distinguishing between OA and any other joint group was 80%. The classification accuracy by sampling day was 87%. For paired classification tasks, the accuracies by joint were 75% for OA vs. OA Control and 70% for OA vs. Sham. The accuracy for separating horses by group (OA vs. Sham) was 68%. In conclusion, SF IR spectroscopy accurately discriminates traumatically induced OA joints from controls.

Post-traumatic osteoarthritis (PTOA) is a common cause of lameness in the horse. There is no cure, therefore treatments are aimed at reducing pain and improving the joint environment by modifying inflammatory pathways or by viscosupplementation. Here, we report the safety and efficacy of the biolubricant (poly(2-methacryloyloxyethyl phosphorylcholine; pMPC) to mitigate the physical, gross, histological, and biochemical effects of arthritis. We created an osteochondral fragment in the middle carpal joint of one limb in 16 horses to induce PTOA; the contralateral limb served as a sham-operated joint. Two weeks postoperative, half (n = 8) of the horses received a single injection of pMPC in the PTOA joint, while the other half received saline. All sham-operated joints (n = 16) received saline. We conducted clinical evaluations weekly while synovial fluid biomarkers were measured biweekly during the 70-day study period. Subsequently, we performed postmortem gross and histologic analyses. Horses in which PTOA joints were treated with pMPC exhibited mild increases in clinical data, including lameness, effusion, and flexion scores. Similarly, synovial cell count, total protein, and prostaglandin E2 values were higher for pMPC-treated joints. Radiographic changes included significantly higher osteophyte scores in pMPC-treated joints at the terminal timepoint. The biolubricant may demonstrate some chondroprotective effects with lower total erosion scores and higher cartilage glycosaminoglycan content. In summary, when pMPC is administered to PTOA joints, the biolubricant induces a mild inflammatory response but may offer some chondroprotective effects in horses.