Antibiotics (Abx) are widely used to treat bacterial disease in both animals and humans. However, overuse can lead to antimicrobial resistance, which is recognized as a global health concern. Consequently, there is a need for alternative approaches to fight bacterial infections. Our long-term goal is to reduce the use of Abx in veterinary medicine by taking advantage of the antimicrobial properties of mesenchymal stem cells (MSCs) as a biological alternative treatment. In contrast to human medicine, the antimicrobial properties of MSCs from veterinary species are far less explored. We study the therapeutic potential of equine MSCs in equine wound management. Since bacterial infections compromise wound healing in horses, we will use our experience and previously validated model systems to study the antimicrobial properties of equine MSCs in the context of wound healing. Our specific hypothesis is that equine MSC-derived secreted factors exert antimicrobial activities by inhibiting bacterial growth, both directly via the production of antimicrobial peptides and indirectly by boosting host-intrinsic antimicrobial defense systems. To test this, we will determine how equine MSC-derived secreted factors inhibit the growth of bacteria and boost host-intrinsic antimicrobial defense systems, in vitro (Aims 1 & 2) as well as in vivo (Aim 3). Results from this study will allow us to develop evidence-based strategies to (i) reduce the negative impacts of wound infections in horses and (ii) decrease the use of conventional Abx by using MSC-derived secreted factors as a biological alternative therapy, not only in equine medicine, but veterinary medicine in general.