Cell therapy for myopathies
Cell therapy for myopathies laboratory has a long-lasting interest and more than 40 years of research experience in the feld of muscle biology and muscular dystrophy. We identified signals that activate myogenesis in the embryo, discovered the myogenic potential of bone-marrow derived, circulating progenitor cells, identified of a novel population of vessel associated progenitor cells that we termed mesoangioblasts, later characterized as a subset of muscle pericytes. We tested the therapeutic potential of mesoangioblasts in mouse and dog models of muscular dystrophy and completed a phase I/II clinical trial in five Duchenne muscular dystrophy patients who received escalating doses of HLA-matched, donor derived mesoangioblasts.
We are currently optimising the transplantation protocol and have started a new trial with autologous, genetically corrected cells. The juxtaposition of developmental biology with stem cell clinical work characterises our work in the field of molecular medicine.
Cossu G, Fears G, Griffin G, ter Meulen V. 2020. Regenerative Medicine: a long and winding road. The Lancet. 395:1746-1747.
De Luca M, Aiuti A, Cossu G, Palmer M, Pellegrini G, Robey P. 2019. Stem cells find they way to clinics. Nature Cell Biol. 21:801-811.
Benedetti S, Hoshiya H, Uno N, Ragazzi M, et al. 2018. Reversible Immortalisation Enables Genetic Correction and Engineering of Next-Generation Human Artificial Chromosomes for Duchenne Muscular Dystrophy. EMBO Mol Med 10:254-275.
Cossu G, Birchall M, Brown T, De Coppi P et al. 2018. Lancet Commission: Stem Cells and Regenerative Medicine. The Lancet 391:883-910.
Cossu G, Previtali SC, Napolitano S, Cicalese MP, et al. 2015. Intra-arterial transplantation of HLA-matched donor mesoangioblasts in Duchenne Muscular Dystrophy. EMBO Mol. Med. 7,1513-28.
Cappellari O, Benedetti S, Innocenzi A, Tedesco FS et al. . 2013. Dll4 and PDGF-BB convert committed skeletal myoblasts to pericytes without erasing their myogenic memory. Developmental Cell 24, 586-599.
Tedesco FS, Gerli MF, Perani L, Benedetti S, et al.2012. Transplantation of Genetically Corrected Human iPSC-Derived Progenitors in Mice with Limb-Girdle Muscular Dystrophy. Science Translational Medicine 4(140):140ra89.
Dellavalle A, Maroli G, Covarello D, Azzoni E et al. 2011. Pericytes resident in post-natal skeletal muscle differentiate into muscle fibers and generate satellite cells. Nature Comm. 2:499.
Tedesco FS, Hoshiya H, D’Antona G, Gerli MFM et al. 2011. Stem Cell-Mediated Transfer of a Human Artificial Chromosome Ameliorates Muscular Dystrophy. Science Translational Medicine 3:96ra78.
Messina G, Biressi S, Monteverde S, Magli A, et al. 2010. Nfix regulates fetal specific transcription in developing skeletal muscle. Cell 140, 554-566.
Gargioli C, Coletta M, De Grandis F, Cannata SM and Cossu G. 2008. PlGF-MMP9 expressing cells restore microcirculation and efficacy of cell therapy in old dystrophic muscle. Nature Med. 14:973-8.
Dellavalle A, Sampaolesi M, Tonlorenzi R, Tagliafico E etal. 2007. Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nature Cell Biol. 9:255-267.
Cossu G, Tajbakhsh S. 2007. Oriented cell divisions and muscle satellite cell heterogeneity. Cell. 129:859-61.
Sampaolesi, M., Blot, S., D’Antona, G., Grangeret al. 2006. Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature 444:574-9.
Sampaolesi M, Torrente Y, Innocenzi A, Tonlorenzi Ret al. 2003. Cell therapy of alpha-sarcoglycan null dystrophic mice through intra-arterial delivery of mesoangioblasts. Science. 301:487-92.