Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy

P. Rocheteau, L. Chatre, D. Briand, M. Mebarki, G. Jouvion, J. Bardon, C. Crochemore, P. Serrani, P. P. Lecci, M. Latil, B. Matot, P. G. Carlier, N. Latronico, C. Huchet, A. Lafoux, T. Sharshar, M. Ricchetti and F. Chrétien ()
Additional contact information
P. Rocheteau: Institut Pasteur Human Histopathology and Animal Models Unit
L. Chatre: Institut Pasteur, Stem Cells and Development
D. Briand: Institut Pasteur Human Histopathology and Animal Models Unit
M. Mebarki: Institut Pasteur Human Histopathology and Animal Models Unit
G. Jouvion: Institut Pasteur Human Histopathology and Animal Models Unit
J. Bardon: Institut Pasteur Human Histopathology and Animal Models Unit
C. Crochemore: Institut Pasteur, Stem Cells and Development
P. Serrani: Institut Pasteur Human Histopathology and Animal Models Unit
P. P. Lecci: Institut Pasteur Human Histopathology and Animal Models Unit
M. Latil: Institut Pasteur Human Histopathology and Animal Models Unit
B. Matot: NMR Laboratory, Institute of Myology
P. G. Carlier: NMR Laboratory, Institute of Myology
N. Latronico: University of Brescia
C. Huchet: INSERM UMR1087/ CNRS UMR6291, Institut du Thorax, Therassay, Université de Nantes, Faculté des Sciences et des Techniques
A. Lafoux: INSERM UMR1087/ CNRS UMR6291, Institut du Thorax, Therassay, Université de Nantes, Faculté des Sciences et des Techniques
T. Sharshar: Institut Pasteur Human Histopathology and Animal Models Unit
M. Ricchetti: Institut Pasteur, Stem Cells and Development
F. Chrétien: Institut Pasteur Human Histopathology and Animal Models Unit

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract Sepsis, or systemic inflammatory response syndrome, is the major cause of critical illness resulting in admission to intensive care units. Sepsis is caused by severe infection and is associated with mortality in 60% of cases. Morbidity due to sepsis is complicated by neuromyopathy, and patients face long-term disability due to muscle weakness, energetic dysfunction, proteolysis and muscle wasting. These processes are triggered by pro-inflammatory cytokines and metabolic imbalances and are aggravated by malnutrition and drugs. Skeletal muscle regeneration depends on stem (satellite) cells. Herein we show that mitochondrial and metabolic alterations underlie the sepsis-induced long-term impairment of satellite cells and lead to inefficient muscle regeneration. Engrafting mesenchymal stem cells improves the septic status by decreasing cytokine levels, restoring mitochondrial and metabolic function in satellite cells, and improving muscle strength. These findings indicate that sepsis affects quiescent muscle stem cells and that mesenchymal stem cells might act as a preventive therapeutic approach for sepsis-related morbidity.

Date: 2015
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DOI: 10.1038/ncomms10145

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