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Skeletal muscle is the most abundant human tissue. It has a complex structure and some regenerative capacity, supported by a pool of muscle stem cells. Numerous, severe genetic diseases impair skeletal muscle function and regenerative capacity, with the vast majority of them still remaining incurable. Our laboratory (www.tedescolab.org) studies skeletal muscle regeneration, focusing on the development of novel therapies for incurable neuromuscular disorders of childhood. Our work pioneered the use of human artificial chromosomes and induced pluripotent stem (iPS) cells for gene and cell therapies of muscular dystrophies. Recently, we developed the first 3D artificial skeletal muscle entirely derived from patient-specific induced pluripotent stem (iPS) cells, and we showed that it can model severe forms of muscular dystrophy with high fidelity and resolution. Current projects focus on generating advanced human in vitro models of neuromuscular diseases for therapy development, as well as on using small molecules to improve human muscle stem cell delivery to target tissues. During my talk I will recap and review significant achievements of our previous work, and present new unpublished results on advanced human neuromuscular disease modelling and stem cell engineering for muscle gene and cell therapy.
