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Similar to the disease affecting humans, osteoarthritis (OA) is a painful musculoskeletal condition affecting 20% of the adult canine population. Several solutions have been proposed, but the results achieved to date are far from being satisfactory. New approaches, such as intra‐articular delivery of cells (including mesenchymal stromal cells), have been proposed. Among the many sources, the adipose tissue is considered very promising. We evaluated the safety, feasibility, and efficacy of a single intra‐articular injection of autologous and micro‐fragmented adipose tissue (MFAT) in 130 dogs with spontaneous OA. MFAT was obtained using a minimally invasive technique in a closed system and injected in the intra‐ and/or peri‐articular space. Clinical outcomes were determined using orthopedic examination and owners’ scores for up to 6 months. In 78% of the dogs, improvement in the orthopedic score was registered 1 month after treatment and continued gradually up to 6 months when 88% of the dogs improved, 11% did not change, and 1% worsened compared with baseline. Considering the owners’ scores at 6 months, 92% of the dogs significantly improved, 6% improved only slightly, and 2% worsened compared with baseline. No local or systemic major adverse effects were recorded. The results of this study suggest that MFAT injection in dogs with OA is safe, feasible, and beneficial. The procedure is time sparing and cost‐effective. Post injection cytological investigation, together with the clinical evidence, suggests a long‐term pain control role of this treatment. The spontaneous OA dog model has a key role in developing successful treatments for translational medicine. stem cells translational medicine 2018;7:819–828

Abstract. As the majority of gliomas arise through malignant transformation of astrocytes, we aimed at investigating the interaction between malignant glioma cells and astrocytes in a co-culture experimental model. For this purpose we analyzed the expression of genes and proteins involved in tumor promotion and invasion, such as glial fibrillary acidic protein (GFAP), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of MMP-2 (TIMP-2), transforming growth factor-ß1 (TGF-ß1), secreted protein acidic and rich in cysteine (SPARC), and connexin 43 (CX43). Co-cultures of human neural stem cell-derived astrocytes and U87 MG astrocytoma cells were performed in a transwell system. Gene expression was evaluated by real-time RT-PCR, and protein analysis was performed by Western blotting, SDS-zymography, and immunofluorescence. GFAP tended to be up-regulated in astrocytes co-cultivated with U87, suggesting a reactive response induced by glioma cells. CX43 mRNA tended to be down-regulated in co-cultured astrocytes, as well as the nonphosphorylated isoform at the protein level. MMP-2 mRNA tended to be up-regulated, and MMP-2 protein levels were significantly increased in astrocytes co-cultivated with U87. TIMP-2 and SPARC mRNA decreased in astrocytes cocultivated with U87, showing lower expression in glioma cells. By contrast, SPARC protein expression was strongly induced in supernatants of co-cultured astrocytes. TGF-ß1 was not modified. Our results suggest that U87 cells elicit phenotype modifications in the neighbouring resident astrocytes very likely mediated by soluble factors. Glioma/ astrocyte interaction could possibly trigger an astrocyte phenotype modification consistent with a malignant transformation, and favouring a more permissive environment for glioma cells invasion.

BackgroundNon-infectious inflammatory diseases of the canine central nervous system (CNS) are common idiopathic disorders grouped under the term meningoencephalomyelitis of unknown origin (MUO). Ante mortem diagnosis is achieved via assessment of clinical signs, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis, but the definitive diagnosis needs histopathological examination. MUO are mostly considered as autoimmune CNS disorders, so that suppressing the immune reaction is the best management method for patients. Mesenchymal stem cells (MSCs) are under investigation to treat autoimmune and degenerative disorders due to their immunomodulatory and regenerative properties. This study aims to verify the safety, feasibility, and efficacy of MSCs treatment in canine idiopathic autoimmune inflammatory disorders of the CNS.MethodsEight dogs presented with acute onset and rapid progression of multifocal neurological signs were selected to the study. In all patients’ physical and neurological examinations, MRI and CSF analyses were performed. Clinical diagnosis in all cases was MUO. All selected dogs responded initially to immunosuppressive drugs (prednisone and a combination of prednisolone and cytosine arabinoside) but developed undesirable side effects. For all eight dogs, the owners considered euthanasia but accepted cell therapy as a last possibility. Autologous bone marrow MSCs (BMMSCs), isolated, cultured, and expanded, were administered by intrathecal (IT) injection in the cisterna magna intravenously (IV) and by intra-arterial (IA) injection in the right carotid artery. Adverse effects and clinical response were monitored for 6 months up to 2-year follow-up.ResultsThe use of autologous BMMSCs in dogs with MUO was safe for IT, IV, and IA injections. No major short- or long-term adverse effects were registered. All the dogs presented early improvement in their general and neurological conditions, with particular effect on cervical pain. The group of dogs treated by IT+IA administration showed a shorter time of reaction to therapy compared to the group treated by IT+IV administration.ConclusionsMSCs treatment in dogs affected by MOU is safe and feasible. A larger group of dogs is needed to confirm these results as well as CNS histology in order to better understand the underlying mechanisms.

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