Inhibiting Myostatin with Follistatin Improves the Success of Myoblast Transplantation in Dystrophic Mice

Duchenne muscular dystrophy is a recessive disease due to a mutation in the dystrophin gene. Myoblast transplantation permits to introduce the dystrophin gene in dystrophic muscle fibers. However, the success of this approach is reduced by the short duration of the regeneration following the transpl...

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Main Authors: Basma F. Benabdallah, Manaf Bouchentouf, Joel Rousseau, Pascal Bigey, Annick Michaud, Pierre Chapdelaine, Daniel Scherman, Jacques P. Tremblay
Format: Article
Language:English
Published: SAGE Publishing 2008-03-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368908784153913
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spelling doaj-c9dd9d025deb409e85d09370d064785f2020-11-25T03:17:10ZengSAGE PublishingCell Transplantation0963-68971555-38922008-03-011710.3727/096368908784153913Inhibiting Myostatin with Follistatin Improves the Success of Myoblast Transplantation in Dystrophic MiceBasma F. Benabdallah0Manaf Bouchentouf1Joel Rousseau2Pascal Bigey3Annick Michaud4Pierre Chapdelaine5Daniel Scherman6Jacques P. Tremblay7Génétique humaine, Centre de Recherche du CHUL, Québec, CanadaGénétique humaine, Centre de Recherche du CHUL, Québec, CanadaGénétique humaine, Centre de Recherche du CHUL, Québec, CanadaInserm, U640, CNRS, UMR8151, René Descartes Paris 5 University, Faculté des Sciences Pharmaceutiques et Biologiques, Chemical and Genetic Pharmacology Laboratory, Ecole Nationale Suprieure de Chimie de Paris, Paris, FranceGénétique humaine, Centre de Recherche du CHUL, Québec, CanadaOntogénie et reproduction, Centre de Recherche du CHUL, Québec, CanadaInserm, U640, CNRS, UMR8151, René Descartes Paris 5 University, Faculté des Sciences Pharmaceutiques et Biologiques, Chemical and Genetic Pharmacology Laboratory, Ecole Nationale Suprieure de Chimie de Paris, Paris, FranceGénétique humaine, Centre de Recherche du CHUL, Québec, CanadaDuchenne muscular dystrophy is a recessive disease due to a mutation in the dystrophin gene. Myoblast transplantation permits to introduce the dystrophin gene in dystrophic muscle fibers. However, the success of this approach is reduced by the short duration of the regeneration following the transplantation, which reduces the number of hybrid fibers. Our aim was to verify whether the success of the myoblast transplantation is enhanced by blocking the myostatin signal with an antagonist, follistatin. Three different approaches were studied to overexpress follistatin in the muscles of mdx mice transplanted with myoblasts. First, transgenic follistatin/mdx mice were generated; second, a follistatin plasmid was electroporated in mdx muscles, and finally, follistatin was induced in mdx mice muscles by a treatment with a histone deacetylase inhibitor. The three approaches improved the success of the myoblast transplantation. Moreover, fiber hypertrophy was also observed in all muscles, demonstrating that myostatin inhibition by follistatin is a good method to improve myoblast transplantation and muscle function. Myostatin inhibition by follistatin in combination with myoblast transplantation is thus a promising novel therapeutic approach for the treatment of muscle wasting in diseases such as Duchenne muscular dystrophy.https://doi.org/10.3727/096368908784153913
collection DOAJ
language English
format Article
sources DOAJ
author Basma F. Benabdallah
Manaf Bouchentouf
Joel Rousseau
Pascal Bigey
Annick Michaud
Pierre Chapdelaine
Daniel Scherman
Jacques P. Tremblay
spellingShingle Basma F. Benabdallah
Manaf Bouchentouf
Joel Rousseau
Pascal Bigey
Annick Michaud
Pierre Chapdelaine
Daniel Scherman
Jacques P. Tremblay
Inhibiting Myostatin with Follistatin Improves the Success of Myoblast Transplantation in Dystrophic Mice
Cell Transplantation
author_facet Basma F. Benabdallah
Manaf Bouchentouf
Joel Rousseau
Pascal Bigey
Annick Michaud
Pierre Chapdelaine
Daniel Scherman
Jacques P. Tremblay
author_sort Basma F. Benabdallah
title Inhibiting Myostatin with Follistatin Improves the Success of Myoblast Transplantation in Dystrophic Mice
title_short Inhibiting Myostatin with Follistatin Improves the Success of Myoblast Transplantation in Dystrophic Mice
title_full Inhibiting Myostatin with Follistatin Improves the Success of Myoblast Transplantation in Dystrophic Mice
title_fullStr Inhibiting Myostatin with Follistatin Improves the Success of Myoblast Transplantation in Dystrophic Mice
title_full_unstemmed Inhibiting Myostatin with Follistatin Improves the Success of Myoblast Transplantation in Dystrophic Mice
title_sort inhibiting myostatin with follistatin improves the success of myoblast transplantation in dystrophic mice
publisher SAGE Publishing
series Cell Transplantation
issn 0963-6897
1555-3892
publishDate 2008-03-01
description Duchenne muscular dystrophy is a recessive disease due to a mutation in the dystrophin gene. Myoblast transplantation permits to introduce the dystrophin gene in dystrophic muscle fibers. However, the success of this approach is reduced by the short duration of the regeneration following the transplantation, which reduces the number of hybrid fibers. Our aim was to verify whether the success of the myoblast transplantation is enhanced by blocking the myostatin signal with an antagonist, follistatin. Three different approaches were studied to overexpress follistatin in the muscles of mdx mice transplanted with myoblasts. First, transgenic follistatin/mdx mice were generated; second, a follistatin plasmid was electroporated in mdx muscles, and finally, follistatin was induced in mdx mice muscles by a treatment with a histone deacetylase inhibitor. The three approaches improved the success of the myoblast transplantation. Moreover, fiber hypertrophy was also observed in all muscles, demonstrating that myostatin inhibition by follistatin is a good method to improve myoblast transplantation and muscle function. Myostatin inhibition by follistatin in combination with myoblast transplantation is thus a promising novel therapeutic approach for the treatment of muscle wasting in diseases such as Duchenne muscular dystrophy.
url https://doi.org/10.3727/096368908784153913
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