Mesenchymal stem cells in veterinary clinical practice: Evidence from naturally occurring diseases.

Mesenchymal stem cells (MSCs) are increasingly used in veterinary medicine to treat a range of naturally occurring diseases in animals, but strong clinical evidence supporting their effectiveness is mostly limited to specific conditions.

Overview of MSC Applications in Veterinary Medicine

• MSCs and MSC-derived extracellular vesicles (EVs) have been applied in treating naturally occurring diseases in client-owned animals.
• Conditions targeted include musculoskeletal disorders, soft-tissue and oral mucosal conditions, neurological disorders, eye diseases, and internal medicine disorders.
• Most research has been done on horses and dogs, who naturally develop these diseases, making findings clinically relevant.

Musculoskeletal Disorders

• Osteoarthritis in dogs and horses has some of the most robust clinical data supporting the use of MSCs.
• Equine superficial digital flexor tendon injuries also have several controlled or prospective studies demonstrating MSC benefits.
• Other musculoskeletal conditions such as ligament injuries and bone diseases have limited evidence based mainly on smaller pilot studies or case reports.

Other Disorders Treated with MSCs

• Soft-tissue and oral mucosal conditions have been treated with MSCs, but evidence is less substantial.
• Neurological diseases, ophthalmic problems, and internal medicine conditions like inflammatory bowel disease, chronic kidney disease, and respiratory diseases have been explored in pilot studies or early trials.
• The evidence base for these conditions is still weak and requires further validation through well-designed trials.

MSC-Derived Extracellular Vesicles (EVs)

• Application of EVs derived from MSCs in veterinary clinical practice is very recent.
• Preclinical studies show promising results, but clinical validation in animals remains limited.
• Further research is needed to confirm their efficacy and safety compared to direct MSC therapy.

Challenges and Limitations in Current Studies

• There is considerable variability across studies in terms of the source of MSCs (e.g., bone marrow, adipose tissue), cell preparation techniques, dosing regimens, and routes of administration (e.g., local injection vs systemic delivery).
• Outcome measures differ widely, making it difficult to compare results directly or conduct meta-analyses.
• Many studies lack appropriate controls, have small sample sizes, or are retrospective, limiting the strength of the evidence.

Future Directions and Recommendations

• Standardization of MSC preparation, dosing, and administration methods is needed to improve comparability among studies.
• Development of validated, objective outcome measures tailored to specific veterinary diseases would enhance evidence quality.
• More controlled, prospective clinical trials with larger sample sizes are required to confirm efficacy and safety.
• Further exploration of MSC-derived EVs as therapeutic agents is warranted with emphasis on clinical validation.
• Overall, strengthening the translational potential of MSC therapies in veterinary medicine depends on rigorous and standardized clinical research.