ABSTRACT
The possibility to treat Duchenne muscular dystrophy (DMD), a lethal X-linked disorder, through cell therapy with mesenchymal stromal cells (MSCs) has been widely investigated in different animal models. However, some crucial questions need to be addressed before starting human therapeutic trials, particularly regarding its use for genetic disorders. How safe is the procedure? Are there any side effects following mesenchymal stem cell transplantation? To address these questions for DMD the best model is the golden retriever muscular dystrophy dog (GRMD), which is the closest model to the human condition displaying a much longer lifespan than other models. Here we report the follow-up of 5 GRMD dogs, which were repeatedly transplanted with human adipose-derived mesenchymal stromal cells (hASC), derived from different donors. Xenogeneic cell transplantation, which was done without immunosuppression, was well tolerated in all animals with no apparent long-term adverse effect. In the present study, we show that repeated heterologous stem-cell injection is a safe procedure, which is fundamental before starting human clinical trials.
Subject(s)
Adipose Tissue/cytology , Dog Diseases/therapy , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , Muscular Dystrophy, Animal/therapy , Animals , Cells, Cultured , Creatine Kinase/blood , Disease Models, Animal , Dog Diseases/blood , Dogs , Feasibility Studies , Female , Follow-Up Studies , Humans , Immunocompetence , Muscular Dystrophy, Animal/blood , Muscular Dystrophy, Duchenne/blood , Muscular Dystrophy, Duchenne/therapy , Reproducibility of Results , Time Factors , Transplantation, Heterologous , Treatment OutcomeABSTRACT
Here we summarize the clinical history of Ringo, a golden retriever muscular dystrophy (GRMD) dog, who had a mild phenotype despite the absence of muscle dystrophin. Ringo died of cardiac arrest at age 11 and therefore displayed a normal lifespan. One of his descendants, Suflair, born April 2006, also displays a mild course. Dystrophin analysis confirmed total absence of muscle dystrophin in both dogs. Muscle utrophin expression did not differ from severely affected GRMD dogs. Finding what protects these special dogs from the dystrophic degeneration process is now a great challenge that may open new avenues for treatment. But most importantly, the demonstration that it is possible to have a functional muscle, in a medium-large animal even in the absence of dystrophin, brings new hope for Duchenne patients.
