Safety and efficacy of the use of canine multipotent mesenchymal stromal cells in the treatment of Meningoencephalomyelitis of unknown origin of dogs

Abstract

Canine Meningoencephalomyelitis of unknown origin (MUO) is a common, highly debilitating neuroinflammatory disease, and likely of an immune-mediated origin. Affected dogs require aggressive immunosuppressive treatment in the long-term, however, treatment failure and severe adverse effects usually occur. MUO has pathophysiological, clinical and histopathological similarities to Multiple Sclerosis (MS), being a natural experimental model for this disease. Multipotent Mesenchymal Stromal Cells (MSCs) has promising potential treatment of autoimmune, inflammatory and degenerative diseases of the CNS, due to their anti-inflammatory, immunomodulatory and neuroregenerative capacity, besides being easy to obtain and having efficient proliferation in culture. To date there are no clinical studies evaluating the effect of MSCs compared to the use of immunosuppressive drugs in dogs with non-infectious Meningoencephalomyelitis. This study aims to select a lineage of MSCs (derived from adipose tissue (AT-MSCs) or placenta (PMSCs)) through the in vitro expression of neurotrophic factors and anti-inflammatory cytokines, to assess its safety and efficacy through intrathecal (IT) and intravenous (IV) transplantation and to compare to the immunosuppressive treatment of prednisone and cytosine arabinoside in dogs with MUO. Our hypothesis is that transplantation of allogeneic MSCs with the best immunomodulatory and regenerative properties in vitro will promote clinical neurological recovery and decrease inflammatory damage in Magnetic Resonance Imaging (MRI) and Cerebrospinal Fluid (CSF) images of dogs. The results of this study may provide relevant data for a new therapeutic protocol development in dogs with MUO and a natural experimental model of autoimmune meningoencephalomyelitis with translational potential for cellular therapy clinical trials in MS patients. (AU)