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Lack of robust satellite cell activation and muscle regeneration during the progression of Pompe disease

INTRODUCTION: Muscle stem cells termed satellite cells are essential for muscle regeneration. A central question in many neuromuscular disorders is why satellite cells are unable to prevent progressive muscle wasting. We have analyzed muscle fiber pathology and the satellite cell response in Pompe d...

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Autores principales: Schaaf, Gerben J., van Gestel, Tom JM, Brusse, Esther, Verdijk, Robert M., de Coo, Irenaeus FM, van Doorn, Pieter A., van der Ploeg, Ans T., Pijnappel, WWM Pim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625612/
https://www.ncbi.nlm.nih.gov/pubmed/26510925
http://dx.doi.org/10.1186/s40478-015-0243-x
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author Schaaf, Gerben J.
van Gestel, Tom JM
Brusse, Esther
Verdijk, Robert M.
de Coo, Irenaeus FM
van Doorn, Pieter A.
van der Ploeg, Ans T.
Pijnappel, WWM Pim
author_facet Schaaf, Gerben J.
van Gestel, Tom JM
Brusse, Esther
Verdijk, Robert M.
de Coo, Irenaeus FM
van Doorn, Pieter A.
van der Ploeg, Ans T.
Pijnappel, WWM Pim
author_sort Schaaf, Gerben J.
collection PubMed
description INTRODUCTION: Muscle stem cells termed satellite cells are essential for muscle regeneration. A central question in many neuromuscular disorders is why satellite cells are unable to prevent progressive muscle wasting. We have analyzed muscle fiber pathology and the satellite cell response in Pompe disease, a metabolic myopathy caused by acid alpha-glucosidase deficiency and lysosomal glycogen accumulation. Pathology included muscle fiber vacuolization, loss of cross striation, and immune cell infiltration. RESULTS: The total number of Pax7-positive satellite cells in muscle biopsies from infantile, childhood onset and adult patients (with different ages and disease severities) were indistinguishable from controls, indicating that the satellite cell pool is not exhausted in Pompe disease. Pax7/Ki67 double stainings showed low levels of satellite cell proliferation similar to controls, while MyoD and Myogenin stainings showed undetectable satellite cell differentiation. Muscle regenerative activity monitored with expression of embryonic Myosin Heavy Chain was weak in the rapidly progressing classic infantile form and undetectable in the more slowly progressive childhood and adult onset disease including in severely affected patients. CONCLUSIONS: These results imply that ongoing muscle wasting in Pompe disease may be explained by insufficient satellite cell activation and muscle regeneration. The preservation of the satellite cell pool may offer a venue for the development of novel treatment strategies directed towards the activation of endogenous satellite cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-015-0243-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-46256122015-10-30 Lack of robust satellite cell activation and muscle regeneration during the progression of Pompe disease Schaaf, Gerben J. van Gestel, Tom JM Brusse, Esther Verdijk, Robert M. de Coo, Irenaeus FM van Doorn, Pieter A. van der Ploeg, Ans T. Pijnappel, WWM Pim Acta Neuropathol Commun Research INTRODUCTION: Muscle stem cells termed satellite cells are essential for muscle regeneration. A central question in many neuromuscular disorders is why satellite cells are unable to prevent progressive muscle wasting. We have analyzed muscle fiber pathology and the satellite cell response in Pompe disease, a metabolic myopathy caused by acid alpha-glucosidase deficiency and lysosomal glycogen accumulation. Pathology included muscle fiber vacuolization, loss of cross striation, and immune cell infiltration. RESULTS: The total number of Pax7-positive satellite cells in muscle biopsies from infantile, childhood onset and adult patients (with different ages and disease severities) were indistinguishable from controls, indicating that the satellite cell pool is not exhausted in Pompe disease. Pax7/Ki67 double stainings showed low levels of satellite cell proliferation similar to controls, while MyoD and Myogenin stainings showed undetectable satellite cell differentiation. Muscle regenerative activity monitored with expression of embryonic Myosin Heavy Chain was weak in the rapidly progressing classic infantile form and undetectable in the more slowly progressive childhood and adult onset disease including in severely affected patients. CONCLUSIONS: These results imply that ongoing muscle wasting in Pompe disease may be explained by insufficient satellite cell activation and muscle regeneration. The preservation of the satellite cell pool may offer a venue for the development of novel treatment strategies directed towards the activation of endogenous satellite cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-015-0243-x) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-28 /pmc/articles/PMC4625612/ /pubmed/26510925 http://dx.doi.org/10.1186/s40478-015-0243-x Text en © Schaaf et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Schaaf, Gerben J.
van Gestel, Tom JM
Brusse, Esther
Verdijk, Robert M.
de Coo, Irenaeus FM
van Doorn, Pieter A.
van der Ploeg, Ans T.
Pijnappel, WWM Pim
Lack of robust satellite cell activation and muscle regeneration during the progression of Pompe disease
title Lack of robust satellite cell activation and muscle regeneration during the progression of Pompe disease
title_full Lack of robust satellite cell activation and muscle regeneration during the progression of Pompe disease
title_fullStr Lack of robust satellite cell activation and muscle regeneration during the progression of Pompe disease
title_full_unstemmed Lack of robust satellite cell activation and muscle regeneration during the progression of Pompe disease
title_short Lack of robust satellite cell activation and muscle regeneration during the progression of Pompe disease
title_sort lack of robust satellite cell activation and muscle regeneration during the progression of pompe disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625612/
https://www.ncbi.nlm.nih.gov/pubmed/26510925
http://dx.doi.org/10.1186/s40478-015-0243-x
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