Advancing mesenchymal stem cell therapy for kidney diseases in companion animals: from mechanisms to clinical application.

Acute and chronic kidney diseases are major clinical challenges in companion animals, yet therapeutic options for reversing established injury remain limited. Mesenchymal stem cells (MSCs) have emerged as a promising therapy due to their immunomodulatory and tissue-repair properties. This review synthesizes current evidence on MSC therapy for kidney disease in cats and dogs, with a focus on mechanisms, preconditioning strategies, delivery routes, and clinical outcomes. Key findings indicate that MSCs exert renoprotective effects primarily through paracrine-mediated immunomodulation rather than direct differentiation. Intravenous administration, while simple, results in >80% pulmonary entrapment and renal homing below 5%; arterial or local injection increases homing to 15-20% but carries procedural risks and lacks standardized dosing. Preconditioning strategies (hypoxia, melatonin, ATRA) enhance MSC survival and homing in rodent models, but feline- and canine-specific validation remains limited. Clinical data from 19 studies in cats/dogs demonstrate that MSC therapy is generally safe, with most adverse events being infusion-related and transient. In feline CKD, consistent trends toward improved glomerular filtration rate and quality of life are reported, although statistical significance is rarely achieved. In canine AKI, MSC therapy improves survival and renal function, but results are heterogeneous and predominantly derived from experimentally induced models. Major evidence gaps include lack of dose standardization, variable MSC characterization, short follow-up durations, and limited long-term safety data. Moving forward, establishing consensus on weight-based dosing, MSC characterization standards, and multicenter randomized controlled trials in naturally occurring disease is essential to translate preclinical promise into clinical practice.