Immune Activated Cellular Therapy for Drug Resistant Infections: Rationale, Mechanisms, and Implications for Veterinary Medicine

SIMPLE SUMMARY: Mesenchymal stromal/stem cells have intrinsic antimicrobial properties, thus making them attractive as an alternative treatment strategy in chronic, drug-resistant bacterial infections. Recent evidence has suggested that these antimicrobial effects can be significantly enhanced by immune activation just prior to injection. This review examines the potential role for cellular therapies in treatment of drug resistant infections in veterinary medicine, drawing on insights across species and discussing the therapeutic potential of this approach overall in today’s veterinary patients. ABSTRACT: 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.