Immunoregulatory mechanisms of mesenchymal stem cell therapy in bovine mastitis

Bovine mastitis remains a significant constraint to dairy production worldwide, resulting in substantial economic losses, animal welfare concerns and growing limitations of antimicrobial-based therapies due to antimicrobial resistance and regulatory restrictions. Mesenchymal stem cell (MSC) therapy demonstrates consistent immunomodulatory, antimicrobial and regenerative effects that directly address the complex pathophysiology of bovine mastitis. Across experimental and early clinical studies, MSC administration results in a marked reduction in mammary inflammation, reflected by decreased somatic cell counts, attenuated leukocyte infiltration and suppression of pro-inflammatory cytokines. While bacteriological cure rates vary depending on the pathogen type and disease severity, MSC therapy consistently improves inflammatory resolution and clinical recovery, particularly in cases of acute mastitis. MSC-derived paracrine factors and extracellular vesicles support epithelial regeneration, angiogenesis and extracellular matrix remodelling, leading to faster restoration of milk yield, improved milk composition and reduced risk of fibrosis. Clinical studies have reported that both autologous and allogeneic MSCs are well-tolerated in dairy cattle, with no significant local or systemic adverse effects and minimal immunogenicity. Therefore, MSC-based treatments have the potential to reduce reliance on antibiotics and eliminate milk withdrawal periods, offering clear economic and public health benefits. However, therapeutic efficacy is influenced by cell source, route of administration, dosing strategy and mastitis phenotype, underscoring the need for optimized and standardized approaches. Collectively, the available evidence demonstrates that MSC therapy delivers reproducible anti-inflammatory and regenerative benefits in bovine mastitis, representing a viable antimicrobial-sparing strategy, particularly when integrated with conventional treatments in chronic or recurrent cases.