Lack of robust satellite cell activation and muscle regeneration during the progression of Pompe diseaseReport as inadecuate

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Acta Neuropathologica Communications

, 3:65

First Online: 28 October 2015Received: 03 September 2015Accepted: 08 October 2015


IntroductionMuscle 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.

ResultsThe 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.

ConclusionsThese 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.

KeywordsPompe disease Satellite cells Pax7 Muscle regeneration Metabolic myopathy Acid alpha glucosidase GAA Electronic supplementary materialThe 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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Author: Gerben J. Schaaf - Tom JM van Gestel - Esther Brusse - Robert M. Verdijk - Irenaeus FM de Coo - Pieter A. van Doorn - A


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