Direct myocardial implantation of human embryonic stem cells in a dog model of Duchenne cardiomyopathy reveals poor cell survival in dystrophic tissue

Abstract

Duchenne muscular dystrophy is characterized by progressive muscle weakness and early death resulting from dystrophin deficiency. Spontaneous canine muscular disorders are interesting settings to evaluate the relevance of innovative therapies in human using pre-clinical trials. One of them, muscular dystrophy in Golden Retrievers (GRMD dogs) provides a powerful animal model of Duchenne muscular dystrophy, mimicking the human cardiac phenotype. They develop mild fibrosis which then degenerates into calcified fibrosis and later with age ventricular dysfunctions. Our goal was to test whether such a cardiac environment was proper for human embryonic stem cell (hESC)-derived cardiac progenitor engraftment and differentiation. For that purpose we have grafted young GRMD dogs with cardiac progenitors derived from hESC, using direct epicardial implantation under immunosupression. Our main result is that dystrophic tissue is not suitable for direct epicardial hESC injection.

Keywords

• Duchenne Muscular Dystrophy
• Human Embryonic Stem Cells
• Golden Retriever Muscular Dystrophy
• Transplantation