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 stemstromal 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 SIGNIFICANCE STATEMENTStudies in veterinary medicine which have employed companion animals to evaluate safety and efficacy of stem cells have not been systematically reviewed for the human medical and biomedical research community. The goal of this review is to shed light on examples whereby companion animal spontaneous disease models (i.e., veterinary patients) were utilized to study novel stem cell therapies, and to stimulate further discussion on the potential value of these models in multidisciplinary studies for the dual benefit of human and veterinary medicine.

Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells

“…Dogs develop many of the same inflammatory and autoimmune diseases as humans and thus clinical studies of stem cell therapy in these canine models can be particularly informative with respect to safety and potential efficacy, in time frames much accelerated compared to human studies [64].…”

Implications for a Stem Cell Regenerative Medicine Based Approach to Human Intervertebral Disk Degeneration

“…Interestingly, the canine breed Dachshund is commonly afflicted with disc degeneration and disc herniation in a manner similar to humans (Hoffman and Dow, 2016). Like humans, afflicted canines can show back pain, impaired movement, or near paralysis.…”

“…Like humans, afflicted canines can show back pain, impaired movement, or near paralysis. In several studies using mesenchymal stem cells injected into affected discs, treated canines showed improvement, including reduced pain, ataxia, improved reflexes, and neurologic-locomotory recovery although surprisingly there did not appear to be any ultrastructural changes as monitored by MRI (reviewed in Hoffman and Dow, 2016). This underscores the utility of using an animal model (canine or bovine Kraus et al, 2017) which are more similar to human and also indicates that the criteria for stem cell mediated clinical success of disc disease might be focused on alleviation of symptoms and recovery of normal activity rather than ultrastructural changes in the spine as assayed by MRI.…”

Mesenchymal Stem Cells as Therapeutic Candidates for Halting the Progression of Diabetic Nephropathy

“…Several diseases have been reported mainly in dogs, but also in cats, and include the chronic kidney disease (CKD) model. The majority of these studies, although uncontrolled, reported that MSCs are potential candidates for regenerating the damaged tissue, as reviewed by Hoffman and Dow [72]. …”