Cardiac dystrophic mesoangioblasts: Molecular characterization of in vitro and in vivo differentiation

In muscular dystrophies a cardiac involvement represents a complication leading the patients to a more dramatic worsening of health condition. Limb-girdle muscular dystrophy type 2E (LGMD 2E) is caused by mutations in the beta sarco-glycan gene. The expression of the sarcoglycan complex is necessary for the stabilization of dystrophin at the sar-colemma level: if this link is interrupted, skeletal and cardiac myofibres degenerate. Recently, we showed that a class of vessel associated stem cells, named mesoangioblasts, isolated from muscle biopsies of mice, dogs and humans can regenerate skeletal fibres in dystrophic subjects. Moreover, wild-type cardiac mesoangioblasts can efficiently differentiate in vitro an in vivo into cardiomyocytes. We isolated and characterized cardiac mesoangioblasts (cdMABs) from heart biopsies of a mouse model of LGMD 2E. In particular, we evaluated the expression of surface markers and cardiac transcription factors and we tested the ability to migrate into heart and filter organs, after intravenous delivery into cardiomyopathic mice. Despite their ability to home and differentiate into cardiomyocytes, cdMABs fail to regenerate necrotic areas of the myocardium. By real time expression array, their transmigration and trans-differentiation ability seems affected by signal-transduction pathways, such as Notch and Wnt signalling, that drive cell fate. Exploring the balancing patterns of these molecular signals will probably shed new light on myogenic program and dystrophy therapy.