Concise Review: Stem Cell Trials Using Companion Animal Disease Models.

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.

Cytosine arabinoside constant rate infusion without subsequent subcutaneous injections for the treatment of dogs with meningoencephalomyelitis of unknown origin.

BACKGROUND: The administration of cytosine arabinoside (CA) by continuous rate infusion (CRI) at the time of diagnosis has been shown to improve the 3-month survival of dogs diagnosed with meningoencephalomyelitis of unknown origin (MUO), compared to subcutaneous administration. The benefit of administering subsequent sequential CA subcutaneous injections is unknown. This study compares the outcomes of a CA CRI protocol with (CRI+subcutaneous group) or without (CRI group) follow-up CA subcutaneous injections; both groups received adjunctive prednisolone. METHODS: Forty-two dogs diagnosed with MUO were recruited (CRI group) and compared with 41 historical control dogs (CRI+subcutaneous group) in a prospective, controlled clinical trial with 36 months of follow-up. RESULTS: Success rates were respectively 64.3 per cent and 65 per cent in the CRI and the CRI+subcutaneous groups at 40 weeks following diagnosis, and 32.5 per cent and 35.9 per cent at 36 months following diagnosis. The median time to relapse was 299 and 285 days for the CRI and the CRI+subcutaneous groups, respectively. No statistically significant difference was found (P≥0.05). CONCLUSION: No clear benefit was identified in the administration of subsequent sequential CA subcutaneous injections after the first administration of CA by CRI for the treatment of dogs diagnosed with MUO.

Glioma Mimics: Magnetic Resonance Imaging Characteristics of Granulomas in Dogs.

Granulomas can "mimic" gliomas on magnetic resonance imaging (MRI) in human patients. The goal of this retrospective study was to report canine brain granulomas that were consistent with glioma based upon MRI, report their histologic diagnosis, and identify MRI criteria that might be useful to distinguish granuloma from glioma. Ten granulomas, initially suspected to be glioma based on MRI, were ultimately diagnosed as granulomatous meningoencephalomyelitis (n = 5), infectious granulomas (n = 3) or other meningoencephalitis (n = 2). Age was 1.6-15.0 years and two dogs were brachycephalic breeds. MRI characteristics overlapping with glioma included intra-axial, heterogeneous, T2-weighted hyperintense, T1-weighted hypointense to isointense mass lesions with contrast-enhancement. Signals on fluid attenuation inversion recovery, gradient echo and diffusion weighted imaging also matched glioma. Peri-lesional edema and mass effect were toward the high end of findings reported for glioma. MRI characteristics that would be considered unusual for glioma included dural contact (n = 4), T2-hypointensity (n = 2), concomitant meningeal-enhancement (n = 9), and minor changes in the contralateral brain (n = 2). Cerebrospinal fluid analysis revealed albuminocytological dissociation or mild pleocytosis. These cases show that granulomas can "mimic" glioma on canine brain MRI. In individual cases, certain MRI findings may help increase the index of suspicion for granuloma. Lack of pronounced cerebrospinal fluid pleocytosis does not exclude granuloma. Signalment is very useful in the suspicion of glioma, and many of these dogs with granuloma were of ages and breeds in which glioma is less commonly seen.

Clinical presentation, diagnostic findings, prognostic factors, treatment and outcome in dogs with meningoencephalomyelitis of unknown origin: A review.

Meningoencephalomyelitis of unknown origin (MUO) encompasses a group of idiopathic, most likely immune mediated, inflammatory central nervous system diseases that cause clinical, diagnostic and treatment challenges to veterinary neurologists. Clinical criteria for obtaining this presumptive diagnosis are currently available, and multiple treatment protocols have previously been investigated in small (prospective or retrospective) case series. As this group of diseases is considered fatal if left untreated, the identification of clinically usable prognostic indices could be of great value. This review provides an overview of recent developments in the clinical presentation, diagnostic findings, possible prognostic factors, treatment and outcome in dogs diagnosed with MUO.

Perspectives on meningoencephalomyelitis of unknown origin.

Meningoencephalomyelitis of unknown origin (MUO) is a heterogeneous group of overlapping central nervous system inflammatory diseases of unknown cause. This article highlights the current understanding of MUO and its phenotypic variants encountered in clinical practice. Diagnostic evaluation of presumptive MUO includes lesion distribution on magnetic resonance imaging and ruling out other acquired diseases. Recent evidence provides further knowledge of immune-mediated processes that underlie the pathogenesis of MUO. Current empiric treatment options include corticosteroids and other adjunctive immunomodulating therapies. As the understanding of neuroimmunology and genetic influences on these disorders evolves, a more targeted treatment approach is becoming attainable.

Status epileticus em decorrência da meningoencefalite granulomatosa em cão / Status epileticus as a result in granulomatous meningoencephalitis in a dog

Meningoencefalite granulomatosa (MEG) é uma condição inflamatória do sistema nervoso central (SNC) de causa idiopática e ocorrência esporádica. A lesão pode ser disseminada, focal ou ocular e foi descrita primeiramente por Braund, Vandevelde e Walker em 1978. Afeta principalmente cães de raças toy como poodles e terriers, mas, também, pode ser vista em cães maiores. É principalmente uma doença de cães jovens a meia idade (de 1 a 8 anos), mas pode ocorrer em qualquer idade (BRAUND, 1985; ETTINGER et al, 2004; MUÑANA et al, 1998;). Alguns estudos não identificaram tais predileções (THOMAS, 1998). Foi atendido em uma clinica veterinária situada em Santa Maria (RS) um canino, fêmea, cor preta, raça Labrador Retriever, seis anos de idade e pesando 35 kg. O animal chegou à clínica com o relato de que havia convulsionado várias vezes até chegar ao consultório.