My research is focused on the study of muscle regeneration, using in vitro and in vivo models of muscle disorders. I am also developing novel gene and cell therapy strategies for muscle disorders by means of human artificial chromosomes, induced pluripotent stem (iPS) cells and biomaterials. I am interested in understanding how skeletal muscle sustains tissue regeneration and how we can improve this process for incurable diseases such as muscular dystrophies.
Our work was the first to show safe and efficacious pre-clinical gene replacement therapy with a human artificial chromosome into an animal model of a genetic disease (specifically, Duchenne muscular dystrophy). We were also amongst the first to report on the therapeutic potential of disease-specific (i.e. limb-girdle muscular dystrophy 2D) iPS cells that have been genetically corrected, transplanted back into an ad hoc generated mouse model and shown to provide therapeutic potential. I am working towards the clinical translation of these strategies into future therapeutic tools for muscle disorders.
We have recently developed the first human iPSC-based 3D model of skeletal muscle laminopathies (Maffioletti SM et al., Cell Reports 2018; Steele-Stallard HB et al., Front Physiol 2018)
Intgrate techniques and expertise of the COST laminopathy network in the aforementioned laminopathy 3D muscle platform. I would like to register as a member of Cost Action CA15214.
Gerli MFM, Moyle LA, Benedetti S, Ferrari G, Ucuncu E, Ragazzi M, Constantinou C, Louca I, Sakai H, Ala P, De Coppi P, Tajbakhsh P, Cossu G, Tedesco FS*. Combined Notch and PDGF Signalling Enhances Migration and Expression of Stem Cell Markers while Inducing Perivascular Cell Features in Muscle Satellite Cells. Stem Cell Reports, 2019 Mar 5;12(3):461- 473. doi.org/10.1016/j.stemcr.2019.01.007
Steele-Stallard H, Pinton L, Sarcar, S, Ozdemir T, Maffioletti SM, Zammit PS, Tedesco FS*. Modelling Skeletal Muscle Laminopathies Using Human Induced Pluripotent Stem Cells Carrying Pathogenic LMNA mutations. Frontiers in Physiology, 2018 Oct 15 doi.org/10.3389/fphys.2018.01332
Maffioletti SM, Sarcar S, Henderson ABH, Mannhardt I, Pinton L, Moyle LA, Steele-Stallard H, Cappellari O, Wells KE, Ferrari G, Mitchell JS, Tyzack GE, Kotiadis VN, Khedr M, Ragazzi M, Wang W, Duchen MR, Patani R, Zammit P, Wells D, Eschenhagen T, Tedesco FS*. Three-dimensional Human iPSC-derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering. Cell Reports 2018 Apr 17;23(3):899-908. doi: 10.1016/j.celrep.2018.03.091.
Benedetti S, Uno N, Hoshiya H, Ragazzi M, Ferrari G, Kazuki Y, Moyle LA, Tonlorenzi R, Lombardo A, Chaouch A, Mouly V, Moore M, Popplewell L, Kazuki K, Katoh M, Naldini L, Dickson G, Messina G, Oshimura M, Cossu G, Tedesco FS*. Reversible Immortalisation Enables Genetic Correction of Human Muscle Progenitors and Engineering of Next-Generation Human Artificial Chromosomes for Duchenne Muscular Dystrophy. EMBO Molecular Medicine, 2017 Dec 14. doi: 10.15252/emmm.201607284.
Maffioletti SM, Gerli MFM, Ragazzi M, Dastidar S, Benedetti S, Loperfido M, Vandendriessche T, Chuah M, Tedesco FS*. Efficient Derivation and Inducible Differentiation of Expandable Skeletal Myogenic Cells from Human ES and Patient-Specific iPS Cells. Nature Protocols, 2015 Jun 4; 10, 941–958 (Cover Article)