P3.26 Local and systemic transplantation of human adipose-derived stem cells into the GRMD dog

Progressive muscular dystrophies (PMD) are an untreatable group of disorders characterized by progressive degeneration of skeletal muscle caused by the absence or defective muscular proteins. The possibility to restore the faulty muscle protein and improve muscle function through cell therapy is a promising approach for the treatment of PMD. Different animal models are available for pre-clinical studies; however the only animal model that reproduces the full spectrum of human pathology is the Golden Retriever Muscular Dystrophy (GRMD) dog, a model for Duchenne Muscular Dystrophy. Affected animals carry a mutation that predicts a premature termination codon in exon 8 and a peptide that is 5% the size of normal dystrophin. These dogs present clinical signs within the first weeks of life involving the limbs as well as masticatory muscles. Diaphragmatic and intercostal muscles impairment leads to progressive respiratory failure. Here we have injected human adipose-derived stem cells (hADSC) intravenously, without immunosuppression, into GRMD dogs. We show that hASCs are able to reach, engraft and fuse to the host GRMD dystrophic muscle. Interestingly, we found a strong band of human dystrophin by WB, but a modest number of labeled fibers by IF. Additional studies are currently underway to better define the localization of human dystrophin at the GRMD muscles. We are also comparing the effect of local injections of canine versus human ASCs. These results may have important applications for future therapy in patients with different forms of muscular dystrophies.