Evaluation of stem-cell therapies in companion animal disease models: a concise review (2015-2023)

Companion animals in veterinary medicine develop multiple naturally occurring diseases analogous to human conditions. We previously reported a comprehensive review on the feasibility, safety, and biologic activity of using novel stem cell therapies to treat a variety of inflammatory conditions in dogs and cats (2008-2015) [Hoffman AM, Dow SW. Concise review: stem cell trials using companion animal disease models. Stem Cells. 2016;34(7):1709-1729. https://doi.org/10.1002/stem.2377]. The purpose of this review is to provide an updated summary of current studies in companion animal disease models that have evaluated stem cell therapeutics that are relevant to human disease. Here we have reviewed the literature from 2015 to 2023 for publications on stem cell therapies that have been evaluated in companion animals, including dogs, cats, and horses. The review excluded case reports or studies performed in experimentally induced models of disease, studies involving cancer, or studies in purpose-bred laboratory species such as rodents. We identified 45 manuscripts meeting these criteria, an increase from 19 that were described in the previous review [Hoffman AM, Dow SW. Concise review: stem cell trials using companion animal disease models. Stem Cells. 2016;34(7):1709-1729. https://doi.org/10.1002/stem.2377]. The majority of studies were performed in dogs (n = 28), with additional studies in horses (n = 9) and cats (n = 8). Disease models included those related to musculoskeletal disease (osteoarthritis and tendon/ligament injury), neurologic disease (canine cognitive dysfunction, intervertebral disc disease, spinal cord injury) gingival/dental disease (gingivostomatitis), dermatologic disease (atopic dermatitis), chronic multi-drug resistant infections, ophthalmic disease (keratoconjunctivitis sicca, eosinophilic keratitis, immune-mediated keratitis), cardiopulmonary disease (asthma, degenerative valve disease, dilated cardiomyopathy), gastrointestinal disease (inflammatory bowel disease, chronic enteropathy), and renal disease (chronic kidney disease). The majority of studies reported beneficial responses to stem cell treatment, with the exception of those related to more chronic processes such as spinal cord injury and chronic kidney disease. However, it should also be noted that 22 studies were open-label, baseline-controlled trials and only 12 studies were randomized and controlled, making overall study interpretation difficult. As noted in the previous review, improved regulatory oversight and consistency in manufacturing of stem cell therapies are needed. Enhanced understanding of the temporal course of disease processes using advanced-omics approaches may further inform mechanisms of action and help define appropriate timing of interventions. Future directions of stem-cell-based therapies could include use of stem-cell-derived extracellular vesicles, or cell conditioning approaches to direct cells to specific pathways that are tailored to individual disease processes and stages of illness. Graphical Abstract