Use of Biologics and Stem Cells in the Treatment of Other Inflammatory Diseases in the Horse.

Mesenchymal stem cells (MSCs) are powerful immunomodulatory cells that act via multiple mechanisms to coordinate, inhibit, and control the cells of the immune system. MSCs act as rescuers for various damaged or degenerated cells of the body via (1) cytokines, growth factors, and signaling molecules; (2) extracellular vesicle (exosome) signaling; and (3) direct donation of mitochondria. Several studies evaluating the efficacy of MSCs have used MSCs grown using xenogeneic media, which may reduce or eliminate efficacy. Although more research is needed to optimize the anti-inflammatory potential of MSCs, there is ample evidence that MSC therapeutics are worthy of further development.

The Potential of Mesenchymal Stem Cells to Treat Systemic Inflammation in Horses.

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. Examples include conditions associated with overwhelming acute inflammatory response such as systemic inflammatory response syndrome to chronic diseases characterized by a prolonged low level of inflammation such as equine asthma and recurrent uveitis. For the acute inflammatory response processes, there is often high morbidity and mortality with no effective immunomodulatory treatment to prevent the overwhelming synthesis of proinflammatory mediators. For chronic inflammatory disease processes, frequently long-term corticosteroid treatment is the therapeutic mainstay, with serious potential complications. Thus, there is an unmet need for alternative anti-inflammatory treatments for both acute and chronic illnesses in horses. While MSCs show promise for such conditions, much research is needed before a clinically safe and effective treatment will be available. Optimal MSC tissue source, patient vs. donor source (autologous vs. allogeneic) and cell growth conditions need to be determined for each problem. For immediate use, allogeneic MSC treatments is preferable, but immune tolerance and adequate safety require further study. MSC collection and cryopreservation from horses before they are injured or ill, whether from umbilical cord tissue, bone marrow or adipose might become more widespread. Once these fundamental approaches to treating specific diseases with MSCs are determined, the route of administration, dose and timing of administration also need to be studied. To provide a framework for development of MSC immunomodulatory treatments, this article reviews the current understanding of equine MSC anti-inflammatory and immunomodulatory properties and proposes how MSC therapy may be further developed to treat acute onset systemic inflammatory processes and chronic inflammatory diseases.

Catheter-associated venous air embolism in hospitalized horses: 32 cases.

BACKGROUND: Venous air embolism is a potentially life-threatening complication of IV catheter use in horses. Despite widespread anecdotal reports of their occurrence, few cases have been reported in the literature and the prognosis is currently unknown. HYPOTHESIS/OBJECTIVES: Our objective was to describe the surrounding circumstances, clinical signs, treatment, progression, and outcome of venous air embolism in hospitalized horses. ANIMALS: Thirty-two horses with acute onset of compatible clinical signs associated with IV catheter disconnection or damage. METHODS: Multicenter retrospective study. Data extracted from clinical records included signalment, presenting complaint, catheter details, clinical signs, treatments, and outcome. RESULTS: Most cases resulted from extension set disconnection occurring within approximately 24 hours after catheter placement. In fewer horses, extension set damage was cited as a cause. Common clinical signs included tachycardia, tachypnea, recumbency, muscle fasciculations and agitation, with abnormal behavior including kicking and flank biting. Less commonly, pathological arrhythmias or more severe neurologic signs, including blindness and seizures, were noted. Progression was unpredictable, with some affected horses developing delayed-onset neurologic signs. Mortality was 6/32 (19%), including 2 cases of sudden death and other horses euthanized because of persistent neurologic deficits. Negative outcomes were more common in horses with recorded blindness, sweating or recumbency, but blindness resolved in 5/8 affected horses. CONCLUSIONS AND CLINICAL IMPORTANCE: The prognosis for resolution of clinical signs after air embolism is fair, but permanent neurologic deficits or pathologic cardiac arrhythmias can arise. Unpredictable progression warrants close monitoring. Systematic clinic-based surveillance could provide additional useful information to aid prevention.

Genetic dissection of MHC-associated susceptibility to Lepeophtheirus salmonis in Atlantic salmon.

BACKGROUND: Genetic variation has been shown to play a significant role in determining susceptibility to the salmon louse, Lepeophtheirus salmonis. However, the mechanisms involved in differential response to infection remain poorly understood. Recent findings in Atlantic salmon (Salmo salar) have provided evidence for a potential link between marker variation at the major histocompatibility complex (MHC) and differences in lice abundance among infected siblings, suggesting that MHC genes can modulate susceptibility to the parasite. In this study, we used quantitative trait locus (QTL) analysis to test the effect of genomic regions linked to MHC class I and II on linkage groups (LG) 15 and 6, respectively. RESULTS: Significant QTL effects were detected on both LG 6 and LG 15 in sire-based analysis but the QTL regions remained unresolved due to a lack of recombination between markers. In dam-based analysis, a significant QTL was identified on LG 6, which accounted for 12.9% of within-family variance in lice abundance. However, the QTL was located at the opposite end of DAA, with no significant overlap with the MHC class II region. Interestingly, QTL modelling also revealed evidence of sex-linked differences in lice abundance, indicating that males and females may have different susceptibility to infection. CONCLUSION: Overall, QTL analysis provided relatively weak support for a proximal effect of classical MHC regions on lice abundance, which can partly be explained by linkage to other genes controlling susceptibility to L. salmonis on the same chromosome.