Contacts: Vincent Mouly, Anne Bigot, Kamel Mamchaoui
With the development of innovative therapeutic approaches for neuromuscular diseases, such as gene therapy or genome editing, muscle cells isolated from patients, called myoblasts, represent an ideal in vitro model to assess these approaches. Using such cells allows to diminish the number of animal experimentations, but they also bear the exact mutation of the patient in its own genetic environment.
There are limits to these in vitro approaches: human somatic cells have a limited proliferative capacity regulated by the mitotic clock, and reach replicative senescence after a defined number of divisions. This limit in proliferation is reached even earlier in degenerative diseases. We can neutralize the replicative senescence of human muscle cells by using a double transduction with lentiviral vectors, thus making them immortal.
As of today, the platform for immortalization of human cells of the Institute of Myology had generated over 130 human myoblast cell lines isolated from patients suffering from over 27 different diseases (DMD, LGMD, FSHD, …), as well as from control subjects. Most of the original material has been obtained anonymously according to the legal requirements, in collaboration with MyoBank, affiliated to EuroBioBank.
Because access to muscle biopsies may be limited for some pathologies, we have also developed the immortalization of skin fibroblasts. These immortalized fibroblasts are then transduced by an inducible MyoD, a muscle specific transcription factor, and these myoconverted cells can then form myotubes and express muscle markers just like muscle cells.
Since several years, these cell lines are available to the scientific community on a collaborative basis, and many international laboratories already use them. A subset of these cell lines can also be used under MTAs for the development of therapeutic tools by private partners. Our efforts aim at encourage and facilitate researches on neuromuscular disorders, as well as the development on therapeutic strategies.
Last publications
- HSPB8 frameshift mutant aggregates weaken chaperone-assisted selective autophagy in neuromyopathies. Tedesco B, Vendredy L, Adriaenssens E, Cozzi M, Asselbergh B, Crippa V, Cristofani R, Rusmini P, Ferrari V, Casarotto E, Chierichetti M, Mina F, Pramaggiore P, Galbiati M, Piccolella M, Baets J, Baeke F, De Rycke R, Mouly V, Laurenzi T, Eberini I, Vihola A, Udd B, Weiss L, Kimonis V, Timmerman V, Poletti A. Autophagy. 2023 Aug;19(8):2217-2239. doi: 10.1080/15548627.2023.2179780. Epub 2023 Feb 28. PMID: 36854646 Free PMC article.
- Caveolae and Bin1 form ring-shaped platforms for T-tubule initiation. Lemerle E, Lainé J, Benoist M, Moulay G, Bigot A, Labasse C, Madelaine A, Canette A, Aubin P, Vallat JM, Romero NB, Bitoun M, Mouly V, Marty I, Cadot B, Picas L, Vassilopoulos S. Elife. 2023 Apr 21;12:e84139. doi: 10.7554/eLife.84139. PMID: 37083699 Free PMC article.
- Prime editing strategies to mediate exon skipping in DMD gene. Happi Mbakam C, Roustant J, Rousseau J, Yameogo P, Lu Y, Bigot A, Mamchaoui K, Mouly V, Lamothe G, Tremblay JP. Front Med (Lausanne). 2023 May 25;10:1128557. doi: 10.3389/fmed.2023.1128557. eCollection 2023. PMID: 37305116 Free PMC article.
- Aberrant Adenosine Triphosphate Release and Impairment of P2Y2-Mediated Signaling in Sarcoglycanopathies. Benzi A, Baratto S, Astigiano C, Sturla L, Panicucci C, Mamchaoui K, Raffaghello L, Bruzzone S, Gazzerro E, Bruno C. Lab Invest. 2023 Mar;103(3):100037. doi: 10.1016/j.labinv.2022.100037. Epub 2023 Jan 10. PMID: 36925196
- High-capacity adenovector delivery of forced CRISPR-Cas9 heterodimers fosters precise chromosomal deletions in human cells. Tasca F, Brescia M, Liu J, Janssen JM, Mamchaoui K, Gonçalves MAFV. Mol Ther Nucleic Acids. 2023 Feb 22;31:746-762. doi: 10.1016/j.omtn.2023.02.025. eCollection 2023 Mar 14. PMID: 36937620
- Tetraspanin CD82 Associates with Trafficking Vesicle in Muscle Cells and Binds to Dysferlin and Myoferlin. Fontelonga T, Hall AJ, Brown JL, Jung YL, Alexander MS, Dominov JA, Mouly V, Vieira N, Zatz M, Vainzof M, Gussoni E. Adv Biol (Weinh). 2023 Jul 12:e2300157. doi: 10.1002/adbi.202300157. Online ahead of print. PMID: 37434585
- Bioengineering a miniaturized in vitro 3D myotube contraction monitoring chip to model muscular dystrophies. Rose N, Estrada Chavez B, Sonam S, Nguyen T, Grenci G, Bigot A, Muchir A, Ladoux B, Cadot B, Le Grand F, Trichet L. Biomaterials. 2023 Feb;293:121935. doi: 10.1016/j.biomaterials.2022.121935. Epub 2022 Dec 13. PMID: 36584444
- Cellular and Genomic Features of Muscle Differentiation from Isogenic Fibroblasts and Myoblasts. Benarroch L, Madsen-Østerbye J, Abdelhalim M, Mamchaoui K, Ohana J, Bigot A, Mouly V, Bonne G, Bertrand AT, Collas P. Cells. 2023 Aug 3;12(15):1995. doi: 10.3390/cells12151995. PMID: 37566074 Free PMC article.
- Muscle Specific Promotors for Gene Therapy – A Comparative Study in Proliferating and Differentiated Cells. Dietz J, Jacobsen F, Zhuge H, Daya N, Bigot A, Zhang W, Ehrhardt A, Vorgerd M, Ehrke-Schulz E. J Neuromuscul Dis. 2023;10(4):575-592. doi: 10.3233/JND-221574. PMID: 37270809 Free PMC article.
- Targeting Duchenne muscular dystrophy by skipping DMD exon 45 with base editors. Gapinske M, Winter J, Swami D, Gapinske L, Woods WS, Shirguppe S, Miskalis A, Busza A, Joulani D, Kao CJ, Kostan K, Bigot A, Bashir R, Perez-Pinera P. Mol Ther Nucleic Acids. 2023 Jul 27;33:572-586. doi: 10.1016/j.omtn.2023.07.029. eCollection 2023 Sep 12. PMID: 37637209 Free PMC article.
- Autosomal dominant in cis D4Z4 repeat array duplication alleles in facioscapulohumeral dystrophy. Lemmers RJLF, Butterfield R, van der Vliet PJ, de Bleecker JL, van der Pol L, Dunn DM, Erasmus CE, D’Hooghe M, Verhoeven K, Balog J, Bigot A, van Engelen B, Statland J, Bugiardini E, van der Stoep N, Evangelista T, Marini-Bettolo C, van den Bergh P, Tawil R, Voermans NC, Vissing J, Weiss RB, van der Maarel SM. Brain. 2023 Sep 13:awad312. doi: 10.1093/brain/awad312. Online ahead of print. PMID: 37703328
- Identification of a muscle-specific isoform of VMA21 as a potent actor in X-linked myopathy with excessive autophagy pathogenesis. Cocchiararo I, Cattaneo O, Rajendran J, Chabry F, Cornut M, Soldati H, Bigot A, Mamchaoui K, Gibertini S, Bouche A, Ham DJ, Laumonier T, Prola A, Castets P. Hum Mol Genet. 2023 Sep 26:ddad164. doi: 10.1093/hmg/ddad164. Online ahead of print. PMID: 37756622
- CRISPR-Cas9 KO Cell Line Generation and Development of a Cell-Based Potency Assay for rAAV-FKRP Gene Therapy. Geoffroy M, Pili L, Buffa V, Caroff M, Bigot A, Gicquel E, Rouby G, Richard I, Fragnoud R. Cells. 2023 Oct 12;12(20):2444. doi: 10.3390/cells12202444. PMID: 37887288 Free PMC article.
- CRISPR-Cas9 editing of a TNPO3 mutation in a muscle cell model of limb-girdle muscular dystrophy type D2. Poyatos-García J, Blázquez-Bernal Á, Selva-Giménez M, Bargiela A, Espinosa-Espinosa J, Vázquez-Manrique RP, Bigot A, Artero R, Vilchez JJ. Mol Ther Nucleic Acids. 2023 Jan 11;31:324-338. doi: 10.1016/j.omtn.2023.01.004. eCollection 2023 Mar 14. PMID: 36789274 Free PMC article.
- A homozygous loss of function variant in POPDC3: From invalidating exercise intolerance to a limb-girdle muscular dystrophy phenotype. De Ridder W, de Vries G, Van Schil K, Deconinck T, Mouly V, Straub V, Baets J. Neuromuscul Disord. 2023 May;33(5):432-439. doi: 10.1016/j.nmd.2023.04.003. Epub 2023 Apr.