Thirumala Rao Talluri, Pradeep Nag, Narendra Singh Rathore, Wilfried A Kues, Dharmendra Kumar, Naresh Selokar, Kamlesh Kumari Bajwa, Mohd Matin Ansari, T K Bhattacharya
Mesenchymal stromal cells (MSCs) are heterogeneous, multipotent cell populations that have become one of the most extensively investigated cell types in veterinary regenerative medicine. They can be isolated from a wide range of adult and perinatal tissues and have attracted considerable interest because of their immunomodulatory properties, broad secretory activity, and potential to promote tissue repair. However, increasing evidence indicates that MSCs should not be regarded as a uniform therapeutic product, as their biological behaviour is influenced by tissue source, donor characteristics, manufacturing conditions, and the recipient microenvironment. Likewise, their therapeutic effects are now understood to arise predominantly through dynamic interactions with the host, including inflammatory licensing, immunomodulation, secreted bioactive factors, extracellular vesicles, metabolic exchange, and responses to apoptotic cells, rather than through durable engraftment and direct tissue replacement alone. Although clinical evidence supports the use of selected MSC products in canine osteoarthritis and suggests promise for equine musculoskeletal disorders, most other veterinary applications remain preclinical or investigational. This review critically examines current knowledge of MSC biological identity, tissue-source diversity, molecular mechanisms, therapeutic applications, and comparative translational roles in companion and farm animals. It also discusses the challenges that continue to limit clinical translation, including biological heterogeneity, product characterization, potency assessment, manufacturing standardization, and regulatory considerations, and highlights future directions for the development of safe, effective, and evidence-based MSC therapies in veterinary medicine.