title: Concise Review: Stem Cell Trials Using Companion Animal Disease Models.
abstract: Studies to evaluate the therapeutic potential of stem cells in humans would benefit from more realistic animal models. In veterinary medicine, companion animals naturally develop many diseases that resemble human conditions, therefore, representing a novel source of preclinical models. To understand how companion animal disease models are being studied for this purpose, we reviewed the literature between 2008 and 2015 for reports on stem cell therapies in dogs and cats, excluding laboratory animals, induced disease models, cancer, and case reports. Disease models included osteoarthritis, intervertebral disc degeneration, dilated cardiomyopathy, inflammatory bowel diseases, Crohn's fistulas, meningoencephalomyelitis (multiple sclerosis-like), keratoconjunctivitis sicca (Sjogren's syndrome-like), atopic dermatitis, and chronic (end-stage) kidney disease. Stem cells evaluated in these studies included mesenchymal stem-stromal cells (MSC, 17/19 trials), olfactory ensheathing cells (OEC, 1 trial), or neural lineage cells derived from bone marrow MSC (1 trial), and 16/19 studies were performed in dogs. The MSC studies (13/17) used adipose tissue-derived MSC from either allogeneic (8/13) or autologous (5/13) sources. The majority of studies were open label, uncontrolled studies. Endpoints and protocols were feasible, and the stem cell therapies were reportedly safe and elicited beneficial patient responses in all but two of the trials. In conclusion, companion animals with naturally occurring diseases analogous to human conditions can be recruited into clinical trials and provide realistic insight into feasibility, safety, and biologic activity of novel stem cell therapies. However, improvements in the rigor of manufacturing, study design, and regulatory compliance will be needed to better utilize these models. Stem Cells 2016;34:1709-1729.
authors.affiliation: Regenerative Medicine Laboratory, Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, Grafton, Massachusetts, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hoffman
authors.affiliation: Center for Immune and Regenerative Medicine, Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Dow
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans; D057805:Pets; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*
keywords: Adipose tissue-derived mesenchymal stem cells; Atopic dermatitis; Bone marrow mesenchymal stem cells; Canine furunculosis; Canine perianal fistulas; Canine stem cells; Companion animal disease models; Crohn's fistulitis; Dilated cardiomyopathy; End stage renal disease; Feline chronic kidney disease; Feline stem cells; Granulomatous meningoencephalomyelitis; Inflammatory bowel disease; Intervertebral disc degeneration; Investigational new animal drug; Keratoconjunctivitis sicca; Lymphocytic-plasmocytic colitis; Meningoencephalitis of unknown origin; Mesenchymal stem cell neural lineage; Multiple sclerosis; Naturally occurring disease; Olfactory ensheathing cells; One Health; Osteoarthritis; Rectocutaneous fistulas; Sjogren's syndrome; Spinal cord injury; Spinal disc herniation; Spontaneous disease models