Browsing by Author "Bogers, Sophie Helen"

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    Bone Marrow Mononuclear Cell for Equine Joint Disease
    Everett, James Blake (Virginia Tech, 2020-09-04)
    Osteoarthritis (OA) can be debilitating and career-ending for horses. Current treatments offer temporary and symptomatic relief, but potentially deleterious side effects. Bone marrow mononuclear cells (BMNC) are a rich source of macrophage progenitors that are anti-inflammatory and promote inflammation resolution. The objective of this study was to evaluate the ability of intra-articular BMNC therapy to improve clinical signs of naturally occurring equine OA. Horses presenting with clinical and radiographic evidence of moderate OA in a single joint were randomly assigned to 1 of 3 treatments: saline (negative control), triamcinolone (positive control), or BMNC (treatment group). Horses were subjectively and objectively evaluated for lameness and synovial fluid collected (cytology and cytokine/growth factor quantification) at 0, 7, and 21 days post-injection. Data were analyzed using General Estimating Equations with significance set at P<0.05. There were no adverse effects noted in any treatment group. No significant differences in synovial fluid cytology parameters, objective/subjective lameness scores, nor joint circumference were found between treatment groups at any time point. Within treatment groups, joint circumference did not change over time for saline- and triamcinolone-treated horses. However, joint circumference and objective lameness decreased significantly within BMNC-treated horses between Days 0 and 21 and Days 7 and 21. Lameness improved in saline-treated horses from 0 to 21 days, but did not improve in triamcinolone-treated horses. The decreased lameness and lack of adverse effects in the BMNC-treated horses in our study support a larger clinical trial using BMNC.
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    Cell-Based Therapies for Joint Disease in Veterinary Medicine: What We Have Learned and What We Need to Know
    Bogers, Sophie Helen (Frontiers, 2018-04-16)
    Biological cell-based therapies for the treatment of joint disease in veterinary patients include autologous-conditioned serum, platelet-rich plasma, and expanded or nonexpanded mesenchymal stem cell products. This narrative review outlines the processing and known mechanism of action of these therapies and reviews current preclinical and clinical efficacy in joint disease in the context of the processing type and study design. The significance of variation for biological activity and consequently regulatory approval is also discussed. There is significant variation in study outcomes for canine and equine cell-based products derived from whole blood or stem cell sources such as adipose and bone marrow. Variation can be attributed to altering bio-composition due to factors including preparation technique and source. In addition, study design factors like selection of cases with early vs. late stage osteoarthritis (OA), or with intra-articular soft tissue injury, influence outcome variation. In this under-regulated field, variation raises concerns for product safety, consistency, and efficacy. Cell-based therapies used for OA meet the Food and Drug Administration’s (FDA’s) definition of a drug; however, researchers must consider their approach to veterinary cell-based research to meet future regulatory demands. This review explains the USA’s FDA guidelines as an example pathway for cellbased therapies to demonstrate safety, effectiveness, and manufacturing consistency. An understanding of the variation in production consistency, effectiveness, and regulatory concerns is essential for practitioners and researchers to determine what products are indicated for the treatment of joint disease and tactics to improve the quality of future research.
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    The Chondroid Conundrum: Transpharyngeal Removal of Guttural Pouch Chondroids in Horses
    Cardona, Guillermo Andres (Virginia Tech, 2023-08-18)
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    The effects of bit chewing on gastric emptying and orocecal transit times in clinically normal horses
    Patton, Molly Elizabeth (Virginia Tech, 2023-02-14)
    Small intestinal ileus affects up to half of all horses undergoing small intestinal surgery, leading to prolonged gastrointestinal (GI) transit time which can be life-threatening. Various prokinetic medications have been associated with varying side effects, questionable efficacy, and increased cost. Gum chewing as a form of sham feeding is used as a safe, effective, well-tolerated, and inexpensive way to ameliorate ileus following GI surgery in humans. Bit chewing for horses, an analogous activity, has been shown to significantly decrease GI total transit time (TTT); however, a direct effect of bit chewing on gastric emptying time (GET), small intestinal transit time (SITT), and total orocecal transit time (OCTT) has not been investigated. Our objective was to determine whether bit chewing increased small intestinal motility and decreased GE, SITT, and OCTT in clinically normal horses. Gastrointestinal motility was compared in horses that were bit chewing compared to control conditions (no bit chewing) in a prospective crossover design study using acetaminophen as a marker for GET and video endoscopy (ALICAM) capsules to determine GET, SITT, and OCTT. Bit chewing was well tolerated by all horses with no side effects noted. Bit chewing led to a shorter GET, SITT, and significantly shorter OCTT when compared to the control group (P = 0.015). Median times for bit chewing conditions were as follows: GE 2.86 hr, SITT 3.65 hr, and OCTT 6.15 hr whereas the median times for control conditions were as follows: GE: 5 hr, SITT 4.4 hr, and OCTT 9.92 hr. In summary, bit chewing proves to be a potential tool to hasten the motility of the oral GIT. It is safe, inexpensive, and potentially effective prokinetic treatment to horses suffering from postoperative ileus and further investigation is warranted.
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    Effects of Bit Chewing on Gastric Emptying, Small Intestinal Transit, and Orocecal Transit Times in Clinically Normal Horses
    Patton, Molly E.; Andrews, Frank M.; Bogers, Sophie Helen; Wong, David; McKenzie, Harold C.; Werre, Stephen R.; Byron, Christopher R. (MDPI, 2023-08-04)
    Ileus is a common life-threatening problem in horses, and currently available treatments may be ineffective. The purpose of this study was to determine whether bit chewing, a form of sham feeding, decreases the gastric emptying time (GET), small intestinal transit time (SITT), and total orocecal transit time (OCTT) in clinically normal horses in a prospective crossover study. Nine healthy horses were acclimated and fed a standardized diet. Following 24 h of fasting, self-contained video endoscopy capsules and acetaminophen were administered into the stomach via a nasogastric tube. Each horse underwent experimental (bit chewing for 20 min every 6 h) or control (no bit chewing) conditions, with a 3-week minimum washout period between conditions. The horses were enrolled in either part of the study until all video capsules were retrieved and/or 30 days lapsed. The video capsules were recovered from manure, and GET, SITT, and OCTT were determined from a video analysis. Bit chewing significantly decreased OCTT (p = 0.015) compared to the control conditions. Bit chewing decreased GET and SITT, but the differences were not significant. The mean (median) times determined via the video capsule analysis for the bit-chewing conditions were as follows: GET, 2.34 h (2.86 h); SITT, 3.22 h (3.65 h); and OCTT, 5.13 h (6.15 h), and for the control conditions, they were as follows: GET, 3.93 h (5 h); SITT, 3.79 h (4.4 h); and OCTT, 8.02 h (9.92 h). Bit chewing decreased OCTT in healthy horses. Because this segment of the gastrointestinal tract is frequently affected by ileus, bit chewing may be a safe and inexpensive intervention for that condition in horses. Further investigation in clinical patients with ileus is warranted.
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    Engrafting Horse Immune Cells into Mouse Hosts for the Study of the Acute Equine Immune Responses
    Leeth, Caroline M.; Adkins, Janie; Hay, Alayna N.; Bogers, Sophie Helen; Potter, Ashley; Witonsky, Sharon G.; Zhu, Jing (MDPI, 2021-10-14)
    Immunological studies in the horse are frequently hampered by lack of environmental control, complicated study design, and ethical concerns when performing high risk studies. The purpose of the current study was to investigate the utility of a xenograft model for studying acute equine immune responses. Immunocompromised non obese diabetic (NOD). sudden combined immunodeficiency (scid).gamma-/- (NSG) mice were engrafted with either equine peripheral blood lymphocytes (PBLs) or equine bone marrow to determine an optimal protocol for equine lymphocyte engraftment. We found that both PBL and bone marrow grafts populated the host mice successfully. Bone marrow transplants were technically more challenging and required further processing to retard graft versus host disease. Graft vs host disease was apparent at 28 days post-PBL transfer and 56 days post-bone marrow transfer. The results of these studies support the use of mouse hosts to study acute equine immune responses and that different engraftment techniques can be used depending on the experimental design.
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    In vitro evaluation of equine bone-marrow derived mesenchymal stromal cells to combat orthopedic biofilm infections
    Khatibzadeh, Sarah M. (Virginia Tech, 2023-08-18)
    Infections of fracture fixation implants and synovial structures are a primary cause of complications, increased treatment costs, and mortality in people and horses. Treatment failure is often due to biofilms that are communities of bacteria that are adhered to a surface or to each other and are surrounded in a self-secreted extracellular matrix. The biofilm matrix protects the indwelling bacteria from being killed by antibiotics and the immune system. Biofilms also stimulate chronic inflammation and tissue destruction, including peri-implant osteolysis and subsequent implant failure and chondromalacia with subsequent osteoarthritis. In horses, the resulting lameness, reduced athletic potential, and poor quality of life may necessitate euthanasia. Equine bone marrow-derived mesenchymal stromal cells (MSC) reduce inflammation and promote healing in musculoskeletal injuries and have recently been discovered to have antimicrobial properties. Equine MSC kill planktonic (free-floating) bacteria and prevent biofilm establishment in laboratory models. MSC from mice and people also promote the transition from acute inflammation to tissue regeneration (resolution of inflammation) by secretion of specialized pro-resolving lipid mediators (SPM). Whether equine MSC can disrupt established biofilms of orthopedic pathogens and modulate the inflammatory response to orthopedic biofilms is unknown. Using a novel biofilm-MSC co-culture model, our objectives were two-fold. We investigated whether MSC alone or with amikacin sulfate, an antibiotic used to treat equine orthopedic infections, could reduce biomass, pellicle size, and live bacteria of biofilms of orthopedic infectious agents S. aureus and E. coli. Next, we investigated whether MSC could modulate immune response to S. aureus biofilms by reducing secretion of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMC) and by secreting SPM. MSC demonstrated partial ability to reduce biofilms but performed differently on S. aureus versus E. coli biofilms. Co-culture of biofilms with MSC significantly reduced pellicle area of biofilms of both bacteria, reduced biomass of S. aureus biofilms, and killed live S. aureus bacteria. MSC combined with amikacin also significantly reduced S. aureus biomass to a greater extent compared to amikacin alone. The resolution in detecting differences between groups for E. coli was diminished because of high variation between biofilms treated with MSC between different donors and between control biofilms between experiments. Using the same experimental system, culture of S. aureus biofilms with MSC in the transwell inserts and PBMC in the bottom wells significantly reduced biofilm size compared to untreated biofilms. Co-culture of MSC and PBMC with S. aureus biofilms also significantly increased detection of multiple SPM on lipid chromatography-mass spectrometry compared to MSC or PBMC cultures alone. Using a commercial equine multiplex bead ELISA, multiple inflammatory cytokines and chemokines were increased when S. aureus biofilms were cultured with MSC and PBMC; however, these were not different from untreated biofilms. Our results indicate that the utility of MSC in combating orthopedic biofilm infections lies in their ability to disrupt the biofilm matrix and promote inflammation resolution. These findings support continued investigation into and optimization of the anti-biofilm mechanisms of MSC.
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    Turning Round: Optimizing the Anti-Inflammatory Properties of Equine Bone Marrow Derived Mesenchymal Stem Cells for Osteoarthritis Through Three-Dimensional Culture
    Bogers, Sophie Helen (Virginia Tech, 2017-04-19)
    Osteoarthritis (OA) is a degenerative disease of diarthrodial joints causing pain and loss of joint function. Etiology is heterogeneous, but commonly involves inflammation arising from impairment of normal tissue homeostasis and/or function. A cycle of low-grade inflammation and global tissue degradation causes alteration of tissue morphology and function via primary mechanisms or inability to withstand physiological forces. Current therapies variably ameliorate symptoms but do not modify progression. Mesenchymal stem cells (MSCs) have multi-modal properties but are ineffective in ameliorating equine OA. However, anti-inflammatory activities of bone marrow derived MSCs (BMSCs) are enhanced by three-dimensional spheroid culture so equine BMSC (eBMSC) spheroids could inhibit intra-articular inflammation. The overarching hypothesis is that eBMSCs can be enhanced to produce an allogeneic eBMSC therapy that inhibits intra-articular inflammation. In vitro experiments compared differences in anti-inflammatory phenotype between spheroid and traditionally cultured monolayer eBMSCs, the viability and health of eBMSC spheroids administered through needles, and the effects of allogeneic donor on the anti-inflammatory potential of eBMSC spheroids. A model of equine LPS induced synovitis was used to investigate anti-inflammatory efficacy of spheroid eBMSCs compared to placebo or monolayer eBMSCs in vivo. eBMSCs aggregate into spheroids that have stable stem cell marker expression with increased secretion and gene expression of IL-6 and PGE2, and gene expression of SDF-1 and TSG-6. IFN𝛾 and TNFα were not produced by eBMSC spheroids and IL-10 production varied between individuals. Spheroids maintain higher viability and lower senescence than monolayer eBMSCs after injection through a needle and form in high-throughput culture without detrimental effects on expression of TSG-6, IL-6 and PGE synthases that denote an anti-inflammatory phenotype. Additionally, there is significant variation in this phenotype depending on the eBMSC donor. eBMSC spheroids reduced total nucleated cell counts and objective lameness measurements at peak levels of intra-articular inflammation compared to monolayer cultured eBMSCs in vivo. In summary, spheroids increase anti-inflammatory potential of eBMSCs and are practical for clinical use. Increased anti-inflammatory efficacy was demonstrated in a model of in vivo inflammation. This dissertation provides an understanding of the anti-inflammatory activities of eBMSC spheroids that can be used to develop an OA therapy.