2013 - CTS 2013 Congress

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Oral Communications 4

9.7 - Safety and feasibility of autologus mesenchymal stem cell implantation in twelve dogs with suspected degenerative myelopathy

Presenter: Offer, Zeira, Tavazzano con Villavesco, Italy
Authors: Offer Zeira1,2,3, Erica Ghezzi1,2,3, Letizia Pettinari1,2,3, Stefano Comazzi1,2,3, Martin Konar1,2,3, Chiara Briola1,2,3, Carlo Cantile1,2,3, Marina Aralla1,2,3

Safety and feasibility of autologus mesenchymal stem cell implantation in twelve dogs with suspected degenerative myelopathy

Offer Zeira1,2,3, Erica Ghezzi1,2,3, Letizia Pettinari1,2,3, Stefano Comazzi1,2,3, Martin Konar1,2,3, Chiara Briola1,2,3, Carlo Cantile1,2,3, Marina Aralla1,2,3

1Ospedale Veterinario San Michele, Tavazzano con Villavesco, Italy; 2Department of veterinary science and public health, University of Milan, Milan, Italy; 3Department of veterinary pathology, University of Pisa, Pisa, Italy

 

Canine degenerative myelopathy (DM) is an adult onset neurodegenerative disease that occurs in many breeds. The histopathology is classified as a multisystem central-peripheral axonopathy. Similarities between DM in dog and neurodegenerative diseases such amyotrophic lateral sclerosis (ALS) were discovered. In both cases etiology is unknown although overproduction of antibodies and immune complexes, inflammation and apoptosis, lack of growth factors, cytotoxicity and oxidative stress are possible factors. The use of mesenchymal stem cells (MSCs) in patients with ALS or DM is justified by their high degree of plasticity, the ability to release growth factors and modulate the immune system. This study aims to evaluatethe safety and feasibility of the intrathecal and intravenous administration of autologous MSCs in dogs with suspected DM.
Twelve dogs with chronic and progressive upper motor neuron clinical signs of the pelvic limbs were included in the study. In all the patients radiographs, magnetic resonance imaging (MRI; VetGrande, 0.25T, Esaote, Genova, Italy) and cerebrospinal fluid (CSF) analysis were negative. DNA exam for superoxide dismutase 1 (SOD-1) mutation was positive.  Autologous bone marrow MSCs were isolated from each dog, cultured and expanded. In each dog 1x10(6) MSCs was injected intrathecaly in cisterna magna, 2x10(6) between L5-L6 space and 0.5x10(6) MSCs/kg intravenously. Follow up of six months included monthly clinical evaluation, complete blood and biochemistry work up and neurological evaluation. In all dogs MRI was repeated. Evaluation of immunitary response on blood samples taken before and after 4 and 24h from MSCs administration was accomplished by means of differentials leukocytes counts and lymphocyte subset using flow cytometry (FC) after peripheral blood centrifugation and staining.
MSCs consistently (>98%) expressed their classical surface markers and were negative for lymphocytes and hematopoietic cells. None of the dogs had an injection-related adverse effects. Blood workup and MRI did not reveal changes compared to previous exams nor onset of new neurological pathologies. Neurological evaluation evidenced static clinical signs in two cases. Two dogs died by natural causes and two dogs were euthanized after 6 and 9 months due to owner’s request. Three of them underwent autopsy and DM was confirmed by histology. Six dogs had mild improvement of the hind limb ataxia and are still alive.

Implantation of MSCs in dogs with DM is a feasible and a relatively safe procedure. Clinical relevance of the immunological effects is yet unclear. The results of this study, together with the fact that neurological status and the course of DM is variable among affected dogs, encourage the selection of a greater, statistically more relevant, group of dogs for similar evaluation. Such enlarged study may also increase the possibility to apply results obtained from the canine model in human medicine.

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