Evaluation of an experimental therapy based on bovine mesenchymal stem cell (MSC) secretome for the treatment of endometritis in dairy cows

Endometritis impairs uterine function and reduces reproductive performance in dairy cows. Conventional treatment involves intrauterine antibiotics; however, antimicrobial resistance has become an increasing concern worldwide. Biofactors secreted by mesenchymal stem/stromal cells (MSCs), collectively known as the secretome possess immunomodulatory, anti-apoptotic, angiogenic, and antimicrobial properties and may represent a novel alternative for treating bovine endometritis. This study evaluated the in vitro antimicrobial potential of bovine fetal MSC-derived secretome (sMSC) against Escherichia Coli and assessed the safety and efficacy of sMSC-based therapy in dairy cows. Conditioned media (CM) derived from fetal bone marrow (BM) and adipose tissue (AT) MSCs reduced E. Coli survival by up to 98%. Intrauterine administration of sMSC produced no significant clinical or hematological alterations, demonstrating that the treatment is safe. Cows with clinical endometritis receiving two intrauterine doses of lyophilized sMSC, separated by 14 days, showed lower (P < 0.05) endometrial polymorphonuclear (PMN) counts (~ 47%) and postpartum endometritis grade (EG) (~ 78%) than placebo-treated animals (PCB). Proteomic analysis of lyophilized sMSC revealed that 11% of the total protein content corresponded to secreted protein acidic and cysteine rich (SPARC), a molecule with known roles in tissue repair and immune regulation, which may underlie the observed therapeutic effects. Together, these results indicate that bovine sMSC-derived secretome is a safe and effective therapy for treating bovine endometritis, potentially contributing to a reduction in antibiotics use in dairy cows.