New and creative approaches are required to treat chronic infections caused by increasingly drug-resistant strains of bacteria. One strategy is the use of cellular therapy employing mesenchymal stromal cells (MSC) to kill bacteria directly and to also activate effective host immunity to infection. We demonstrated previously that activated MSC delivered systemically could be used effectively together with antibiotic therapy to clear chronic biofilm infections in rodent models. Therefore, we sought in the current studies to gain new insights into the antimicrobial properties of activated canine MSC and to evaluate their effectiveness as a novel cellular therapy for treatment of naturally-occurring drug resistant infections in dogs. These studies revealed that canine MSC produce and secrete antimicrobial peptides that synergize with most classes of common antibiotics to trigger rapid bactericidal activity. In addition, activated canine MSC migrated more efficiently to inflammatory stimuli, and secreted factors associated with wound healing and fibroblast proliferation and recruitment of activated neutrophils. Macrophages incubated with conditioned medium from activated MSC developed significantly enhanced bactericidal activity. Clinical studies in dogs with chronic multidrug resistant infections treated by repeated i.v. delivery of activated, allogeneic MSC demonstrated significant clinical benefit, including infection clearance and healing of infected tissues. Taken together, the results of these studies provide new insights into antimicrobial activity of canine MSC, and their potential clinical utility for management of chronic, drug-resistant infections.

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. Therefore, the aim of this study was to evaluate the short‐term impact of intravenous (IV) delivery of allogeneic adMSCs in an established model of spontaneous OA, the Hartley guinea pig. Animals with moderate OA received once weekly injections of 2 × 10⁶ adMSCs or vehicle control for 4 weeks in peripheral veins; harvest occurred 2 weeks after the final injection. Systemic administration of adMSCs resulted in no adverse effects and was efficacious in reducing clinical signs of OA (as assessed by computer‐aided gait analysis) compared to control injected animals. Further, there were significant decreases in key inflammatory mediators (including monocyte chemoattractant protein‐1, tumor necrosis factor, and prostaglandin E₂) both systemically (liver, kidney, and serum) and locally in the knee (joint tissues and synovial fluid) in animals treated with IV adMSCs relative to controls (as per enzyme‐linked immunosorbent assay and/or immunohistochemistry, dictated by tissue sample). Thus, systemic administration of adMSCs by IV injection significantly improved gait parameters and reduced both systemic and intra‐articular inflammatory mediators in animals with OA. These findings demonstrate the potential utility of alternative delivery approaches for cellular therapy of OA, particularly for patients with multiple affected joints.

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). The purpose of this review is to summarize the current literature on mechanisms of antimicrobial activity of MSC with emphasis on enhanced effects through receptor agonism, and data supporting use of ACT in treatment of bacterial infections in veterinary species including dogs, cats, and horses with implications for further treatment applications. This review will advance the field’s understanding of the use of activated antimicrobial cellular therapy to treat infection, including mechanisms of action and potential therapeutic applications.

The discovery that a population of cells derived from adult tissues had regenerative properties and could be expanded and utilized therapeutically led to an abundance of research into the safety and efficacy of these cells for a variety of disease processes. Derived from tissues of mesenchymal origin, these cells were called mesenchymal stem cells or mesenchymal stromal cells (MSCs). MSCs were subsequently found to have a variety of anti-inflammatory, antimicrobial, and regenerative properties both in vitro and in vivo. These cells have been extensively studied and demonstrated to be effective in the treatment of autoimmune diseases, inflammatory diseases, infectious diseases, and other pathologic conditions. Multiple veterinary clinical trials have been performed for diseases such as osteoarthritis, soft tissue, and tendon injuries in addition to other inflammatory and infectious conditions. Exotic animal species can pose additional challenges to the treatment of common medical conditions such as osteoarthritis due to varying metabolism and tolerance to medications as well as potential difficulty to medicate or utilize other common forms of therapy such as physical therapy, laser, massage, and acupuncture. Current knowledge of MSC use in exotic species is limited, but there is a large potential for benefit to a variety of species utilizing this novel therapeutic tool. This review includes a brief overview of mechanisms and known applications of this therapy as well as current and potential applications of MSCs in exotic animal species.