“Molecular mechanisms of cardiomyopathy related to muscular dystrophy and stem cell therapy”
Maurilio Sampaolesi was born in Rome, Italy. He obtained a Master in Biological Sciences in 1991 and a PhD in Cardiovascular Pathophysiology in 1996 at the University of Rome, Italy.
The granted project is entitled: “Molecular mechanisms of cardiomyopathy related to muscular dystrophy and stem cell therapy”. In muscular dystrophies a cardiac involvement represent a complication leading the patients to a more dramatic worsening of health condition. In Duchenne muscular dystrophy, Becker muscular dystrophy and, more recently, in some of dystrophinopaties termed sarcoglycanopathies, dilated cardiomyopathy and electrocardiogram abnormalities are frequent findings. The molecular circuits that drive the connection between the muscular dystrophy and the onset of complex cardiac disease are still unknown and our knowledge about that remains primitive.
The project aims to understand the molecular mechanisms of cardiomyopathy related to the sarcoglycan and dystrophin mutations, and to develop a novel stem cell based therapy in mouse models of dilated cardiomyopathy. For the first point of the project, a connection between growth factor-related calcium channel and mutations in sarcoglycans will be considered; primary cardiomyocytes from dystrophic, cardiomyopathic and control mice and dogs will be used as cell model in order to verify their physiological characteristics after stretching and/org drug treatment. For the second point of the project murine, canine and human mesoangioblasts (MABs), a class of vessel-associated stem cells as recently described by Maurilio Sampaolesi (Science 2003; Nature 2006; Nature Cell Biology 2007), will be used to treat respectively beta-sarcoglycan (β-SG) KO mice, scid/beige β-SG KO mice, or GRMD dogs, animal models of dilated cardiomyopathy and muscular dystrophy. The novelty of this project is to establish a molecular link between two hereditary diseases (cardiomyopahty and muscular dystrophy) caused by mutation of sarcoglycan and dystrophin genes. Muscle hypertrophy, that occurs, as compensatory mechanism in the muscular dystrophy as well as in cardiomyophaty is a crucial event leading to a more severe phenotype. Understanding the common compensatory mechanisms is essential for discovering new therapeutic approach. Finally the ultimate goals of the project are to verify the suitability of stem cell therapy in cardiac disease that is such a hot and controversial issue even though so promising.
Maurilio Sampaolesi is an outstanding investigator in the area of mesodermal stem cells with specific interests in skeleltal an cardiac muscle differentiation. He will carry out his research in the Stem Cell Institute Leuven (SCIL) (Univeristy of Leuven). His immediate interest is the application of stem cell therapy in muscular dystrophy, but his research will be of great importance in SCIL interested in stem cells for skeletal as well as cardiac disorders. As the ultimate goal of the development of SCIL is to generate innovative therapies for otherwise untreatable diseases, he is a perfect example of the translational researcher who can fill such a niche.