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. The immunosuppressive activity of the two cell types was evaluated by adding autologous or allogeneic BMDMSCs to activated lymphocytes and assessing suppression of lymphocyte proliferation and IFNγ production. Fifty-six allogeneic and 12 autologous combinations were evaluated. Studies were also done to elucidate mechanisms by which equine mesenchymal stem cells (MSCs) suppress lymphocyte function. Potential mechanisms evaluated included production of prostaglandin E (PGE), nitric oxide, transforming growth factor-beta, and indoleamine 2,3-dioxygenase. We found that autologous and allogeneic BMDMSCs both induced mild but equivalent levels of spontaneous lymphocyte activation in vitro. In in vitro assays assessing the ability of BMDMSCs to suppress activated lymphocytes, both allogeneic and autologous BMDMSCs suppressed T cell proliferation and IFNγ production to an equal degree. The primary mechanism of equine BMDMSC suppression of T cells was mediated by PGE. We concluded that allogeneic and autologous BMDMSCs are equivalent in terms of their immunomodulatory properties, and stimulated peripheral blood mononuclear cells appear to trigger the immunosuppressive properties of MSCs. Therefore, both cell types appear to have equal potency in modulating inflammatory processes related to acute or chronic musculoskeletal injuries in the horse.

Incisional drainage is common following ventral midline laparotomy. The use of a 2-layer, modified subcuticular closure was associated with a significant reduction in the incidence of incisional drainage compared with closure performed with skin sutures, but not closure performed with staples.

The sensitive period is a special time for auditory learning in songbirds. However, little is known about perception and discrimination of song during this period of development. The authors used a go/no-go operant task to compare discrimination of conspecific song from reversed song in juvenile and adult zebra finches (Taeniopygia guttata), and to test for possible developmental changes in perception of syllable structure and syllable syntax. In Experiment 1, there were no age or sex differences in the ability to learn the discrimination, and the birds discriminated the forward from reversed song primarily on the basis of local syllable structure. Similar results were found in Experiment 2 with juvenile birds reared in isolation from song. Experiment 3 found that juvenile zebra finches could discriminate songs on the basis of syllable order alone, although this discrimination was more difficult than one based on syllable structure. The results reveal well-developed song discrimination and song perception in juvenile zebra finches, even in birds with little experience with song.

Objective: To develop a novel technique for left paralumbar laparoscopic bilateral ovariectomy in standing, sedated mares.Study design: Prospective descriptive clinical study.Animals: Twelve client-owned mares.Methods: Healthy mares with normal ovarian palpation and ultrasonographic appearance were enrolled. Horses were restrained in standing stocks and administered a variable rate infusion of sedation. A left paralumbar bilateral ovariectomy was performed with 1 laparoscopic and 3 instrument portals. Access to the right ovary was facilitated by retracting the descending colon and associated mesentery with a fan retractor. Ovaries were removed with traumatic forceps, and a blunt tip vessel sealing device. A laparoscopic portal within the 17th intercostal space provided good visualization of the right ovary and reduced interference between instrumentation. Complications were recorded during hospitalization. In addition, an owner follow-up questionnaire was used to determine complications after discharge from the hospital.Results: Left paralumbar bilateral ovariectomy was successful in all 12 mares, with a mean surgical time of 76 6 8 minutes. Postoperative complications occurred in 4/12 (33%) mares and included fever, mild colic, incisional swelling, and azotemia. Complications resolved and mares returned to full activity, with complete owner satisfaction.Conclusions: Bilateral ovariectomy can be successfully achieved with minimal morbidity in standing mares with normal ovarian ultrasonographic appearance via left paralumbar laparoscopy.

Mesenchymal stem cells (MSCs) are widely used for treatment of musculoskeletal diseases in horses, but there is ongoing debate regarding the relative safety and efficacy of allogeneic MSCs, compared with autologous equine MSCs. This review summarises the currently available published data regarding the therapeutic use of autologous and allogeneic MSCs in horses. Arguments that have been advanced against the use of allogeneic MSCs include higher risk of immunological reactions and shorter cell survival times following injection. Arguments favouring the use of allogeneic MSCs include the ability to bank cells and reduce the time to treatment, to collect MSCs from younger donor animals and the ability to manipulate banked cells prior to administration. In vitro studies and a limited set of experimental in vivo studies have indicated that adverse immunological reactions may occur when allogeneic MSCs are administered to horses. However, newer studies lack evidence of inflammatory reactions or adverse clinical responses when allogeneic MSCs are administered and compared with autologous MSCs. Thus, while the relative merits of allogeneic vs autologous MSCs for treatment of musculoskeletal injuries in horses have not been fully established, accumulating evidence from studies in horses suggests that allogeneic MSCs maybe a safe alternative to autologous MSCs. Large, properly designed, randomised trials in addition to careful immunological evaluation of short‐term and long‐term, local and systemic immune responses are needed to more fully resolve the issue.

Summary Background Allogeneic bone marrow‐derived mesenchymal stem cells (BMDMSCs) could provide multiple advantages over autologous BMDMSCs, including creating an ‘off‐the‐shelf’ treatment together with the ability to control for donor variation. Objectives The objective of the study was to compare the clinical and synovial fluid response of the normal equine joint to autologous and pooled‐allogeneic BMDMSCs while controlling for individual variation and joint variations in response to intra‐articular injections. We hypothesised that, by controlling for individual animal and joint variation, we could identify differences between allogeneic vs. autologous BMDMSCs in noninflamed joints. Study design Randomised‐controlled experiment. Methods Bone marrow was harvested from eight horses. Autologous BMDMSCs were culture expanded, cryopreserved and thawed immediately prior to administration. For allogeneic BMDMSC treatments, four horses' BMDMSCs were culture expanded, pooled, cryopreserved and thawed immediately prior to use. Ten million (autologous or pooled‐allogeneic) BMDMSCs were administered into contralateral forelimb metacarpophalangeal joints so that every autologous and allogeneic injection could be compared within the same animal. Clinical parameters included subjective lameness, objective lameness (Lameness Locator™), response to flexion, joint circumference and joint effusion. Arthrocentesis was performed for assessment of the nucleated cell count, differential cell count, total protein, and synovial concentrations of prostaglandin E2 (PGE2) and c‐reactive protein (CRP). All parameters were measured at baseline, 6, 12, 24, 72, 168 and 336 h post‐injection. Results No difference was detected in any parameters between forelimb metacarpophalangeal joints administered autologous or pooled‐allogeneic BMDMSCs. Main limitations This study did not attempt to measure efficacy of BMDMSCs for musculoskeletal disease and should be followed by properly controlled efficacy trials. Conclusions The study did not identify any clinical or cytological differences in the normal joint response to allogeneic or autologous BMDMSCs. A larger study to prove equivalence is warranted as allogeneic BMDMSCs may be a feasible alternative to autologous BMDMSCs.

Addition of mepivacaine to amikacin for IVRLP in the horse as a means of providing analgesia without decreasing antimicrobial activity.

No abstract