Journal articles
Prednisolone rescues Duchenne muscular dystrophy phenotypes in human pluripotent stem cell–derived skeletal muscle in vitro
Ziad Al Tanoury
1
John Zimmerman
1
Jyoti Rao
1
Daniel Sieiro
1
Harold Mcnamara
1
Thomas Cherrier
1
Alejandra Rodríguez-Delarosa
1
Aurore Hick-Colin
1
Fanny Bousson
1
Charlotte Fugier-Schmucker
1
Fabio Marchiano
2
Bianca Habermann
2
Jérome Chal
1
Alexander Nesmith
1
Svetlana Gapon
1
Erica Wagner
1
Vandana Gupta
1
Rhonda Bassel-Duby
1
Eric Olson
1
Adam Cohen
1
Kevin Kit Parker
1
Olivier Pourquié
1
Harold Mcnamara 1
Author
Thomas Cherrier 1
Author
Alejandra Rodríguez-Delarosa 1
Author
Aurore Hick-Colin 1
Author
Fanny Bousson 1
Author
Charlotte Fugier-Schmucker 1
Author
Fabio Marchiano 2
Author
Bianca Habermann 2
Author
Vandana Gupta 1
Author
Rhonda Bassel-Duby 1
Author
Eric Olson 1
Author ORCID : https://orcid.org/0000-0003-1151-8262
Adam Cohen 1
Author
Kevin Kit Parker 1
Author
Olivier Pourquié 1
Author ORCID : https://orcid.org/0000-0001-5189-1227
1
HMS - Harvard Medical School [Boston] (25 Shattuck Street Boston, MA 02115 - United States)
2
IBDM - Institut de Biologie du Développement de Marseille (Case 907 - Parc Scientifique de Luminy 13288 Marseille Cedex 9 - France)
- AMU - Aix Marseille Université : UMR7288 (Aix-Marseille Université Jardins du Pharo 58 Boulevard Charles Livon 13284 Marseille cedex 7 - France)
- CdF (institution) - Collège de France (France)
- CNRS - Centre National de la Recherche Scientifique : UMR7288 (France)
Abstract : Duchenne muscular dystrophy (DMD) is a devastating genetic disease leading to degeneration of skeletal muscles and premature death. How dystrophin absence leads to muscle wasting remains unclear. Here, we describe an optimized protocol to differentiate human induced pluripotent stem cells (iPSC) to a late myogenic stage. This allows us to recapitulate classical DMD phenotypes (mislocalization of proteins of the dystrophin-associated glycoprotein complex, increased fusion, myofiber branching, force contraction defects, and calcium hyperactivation) in isogenic DMD-mutant iPSC lines in vitro. Treatment of the myogenic cultures with prednisolone (the standard of care for DMD) can dramatically rescue force contraction, fusion, and branching defects in DMD iPSC lines. This argues that prednisolone acts directly on myofibers, challenging the largely prevalent view that its beneficial effects are caused by antiinflammatory properties. Our work introduces a human in vitro model to study the onset of DMD pathology and test novel therapeutic approaches.
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Journal articles
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https://hal-amu.archives-ouvertes.fr/hal-03451593
Contributor : Bianca Habermann Connect in order to contact the contributor
Submitted on : Friday, November 26, 2021 - 3:19:41 PM
Last modification on : Tuesday, January 4, 2022 - 6:46:40 AM
Contributor : Bianca Habermann Connect in order to contact the contributor
Submitted on : Friday, November 26, 2021 - 3:19:41 PM
Last modification on : Tuesday, January 4, 2022 - 6:46:40 AM
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- HAL Id : hal-03451593, version 1
- DOI : 10.1073/pnas.2022960118
- PUBMEDCENTRAL : PMC8285911
Citation
Ziad Al Tanoury, John Zimmerman, Jyoti Rao, Daniel Sieiro, Harold Mcnamara, et al.. Prednisolone rescues Duchenne muscular dystrophy phenotypes in human pluripotent stem cell–derived skeletal muscle in vitro. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2021, 118 (28), pp.e2022960118. ⟨10.1073/pnas.2022960118⟩. ⟨hal-03451593⟩
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