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Biochim Biophys Acta Mol Basis Dis. 2017 Oct;1863(10 Pt B):2546-2553. doi: 10.1016/j.bbadis.2017.04.019. Epub 2017 Apr 27.

A novel paradigm links mitochondrial dysfunction with muscle stem cell impairment in sepsis.

Author information

1
Department of Developmental and Stem Cell Biology, Institut Pasteur, Stem Cells and Development, 75724 Cedex 15, Paris, France; Team Stability of Nuclear and Mitochondrial DNA, CNRS UMR 3525 and UMR 3738, 75724 Cedex 15, Paris, France.
2
Infection and Epidemiology Department, Institut Pasteur, Human Histopathology and Animal Models Unit, 75724 Cedex 15, Paris, France; Department of Anaesthesiology, Critical Care, SMUR, and Burn Unit, GH Saint-Louis-Lariboisière-Fernand Widal University Hospitals, Assistance Publique, Hôpitaux de Paris, Paris, France.
3
Infection and Epidemiology Department, Institut Pasteur, Human Histopathology and Animal Models Unit, 75724 Cedex 15, Paris, France.
4
Infection and Epidemiology Department, Institut Pasteur, Human Histopathology and Animal Models Unit, 75724 Cedex 15, Paris, France; TRIGGERSEP, F-CRIN Network, Versailles 78000, France; Laboratoire de Neuropathologie, Centre Hospitalier Sainte Anne, Paris 75014, France; Paris Descartes University, Sorbonne Paris Cité, Paris 75006, France.
5
Department of Developmental and Stem Cell Biology, Institut Pasteur, Stem Cells and Development, 75724 Cedex 15, Paris, France; Team Stability of Nuclear and Mitochondrial DNA, CNRS UMR 3525 and UMR 3738, 75724 Cedex 15, Paris, France. Electronic address: miria.ricchetti@pasteur.fr.

Abstract

Sepsis is an acute systemic inflammatory response of the body to microbial infection and a life threatening condition associated with multiple organ failure. Survivors may display long-term disability with muscle weakness that remains poorly understood. Recent data suggest that long-term myopathy in sepsis survivors is due to failure of skeletal muscle stem cells (satellite cells) to regenerate the muscle. Satellite cells impairment in the acute phase of sepsis is linked to unusual mitochondrial dysfunctions, characterized by a dramatic reduction of the mitochondrial mass and hyperactivity of residual organelles. Survivors maintain the impairment of satellite cells, including alterations of the mitochondrial DNA (mtDNA), in the long-term. This condition can be rescued by treatment with mesenchymal stem cells (MSCs) that restore mtDNA alterations and mitochondrial function in satellite cells, and in fine their regenerative potential. Injection of MSCs in turn increases the force of isolated muscle fibers and of the whole animal, and improves the survival rate. These effects occur in the context of reduced inflammation markers that also raised during sepsis. Targeting muscle stem cells mitochondria, in a context of reduced inflammation, may represent a valuable strategy to reduce morbidity and long-term impairment of the muscle upon sepsis.

KEYWORDS:

Mesenchymal stem cells; Mitochondria; Mitochondrial DNA; Muscle stem cells; Sepsis

PMID:
28456665
DOI:
10.1016/j.bbadis.2017.04.019
[Indexed for MEDLINE]
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