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Title: Generation of biocompatible human 3D skeletal muscle tissue from healthy and dystrophic pluripotent stem cells
Author: Maffioletti, S. M.
ISNI:       0000 0004 7224 475X
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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Skeletal muscle is a tissue with remarkable regenerative abilities but a wide range of disorders can impair its functions. At present, there is no effective therapy for most of these pathologies and this represents a significant unmet medical need. The pursuit of therapeutic strategies has led to the development of different encouraging approaches. Importantly, tissue engineering is also emerging as a promising discipline for the establishment of new platforms with therapeutic relevance for muscle disorders. Generating human artificial skeletal muscles in vitro would indeed provide an invaluable tool for disease modelling, drug screening and tissue replacement. Nevertheless, skeletal muscle tissue engineering is extremely challenging and at present no commonly endorsed model is available. Specifically, one of the bottlenecks is the use of primary cells, which hold the drawback of scarce availability and reduced proliferation and differentiation potential in vitro thus limiting their use. Here I describe the generation of 3D artificial mini-muscles from human pluripotent stem cells derived from healthy donors and patients with muscular dystrophy. This has never been reported before and the use of pluripotent stem cells offers a virtually unlimited source of myogenic cells. These patient- and disease-specific human artificial mini-muscles recapitulate characteristics of the adult tissue and, importantly, are able to engraft into immunodeficient mice. Finally, I show that other isogenic cell types present in normal muscle tissue (such as endothelial cells and pericytes) can be derived and combined together with the same patient-specific myogenic cells, thus generating a multi-lineage artificial mini-muscle. This complex platform could provide a valuable tool for skeletal muscle disease modelling, drug screening and tissue replacement ultimately leading to the development of new therapies for muscle diseases.
Supervisor: Tedesco, F. S. ; Whitmore, D. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available