title: Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy.
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.
authors.affiliation: Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, 75724 cedex15, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Rocheteau
authors.affiliation: Department of Developmental and Stem Cell Biology, Institut Pasteur, Stem Cells and Development, 75724 cedex15, Paris, France.|Team Stability of Nuclear and Mitochondrial DNA, CNRS UMR 3525, 75724 cedex15, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Chatre
authors.affiliation: Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, 75724 cedex15, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Briand
authors.affiliation: Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, 75724 cedex15, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Mebarki
authors.affiliation: Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, 75724 cedex15, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Jouvion
authors.affiliation: Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, 75724 cedex15, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Bardon
authors.affiliation: Department of Developmental and Stem Cell Biology, Institut Pasteur, Stem Cells and Development, 75724 cedex15, Paris, France.|Team Stability of Nuclear and Mitochondrial DNA, CNRS UMR 3525, 75724 cedex15, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Crochemore
authors.affiliation: Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, 75724 cedex15, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Serrani
authors.affiliation: Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, 75724 cedex15, Paris, France.
authors.forename: P P
authors.initials: PP
authors.lastname: Lecci
authors.affiliation: Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, 75724 cedex15, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Latil
authors.affiliation: NMR Laboratory, Institute of Myology, Paris 75013, France.|CEA, I2BM, MIRCen, NMR Laboratory, Paris 75013, France.
authors.forename: B
authors.initials: B
authors.lastname: Matot
authors.affiliation: NMR Laboratory, Institute of Myology, Paris 75013, France.|CEA, I2BM, MIRCen, NMR Laboratory, Paris 75013, France.
authors.forename: P G
authors.initials: PG
authors.lastname: Carlier
authors.affiliation: Anesthesia and Reanimation Department, Department of Surgery, University of Brescia, Brescia 25121, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Latronico
authors.affiliation: INSERM UMR1087/ CNRS UMR6291, Institut du Thorax, Therassay, Université de Nantes, Faculté des Sciences et des Techniques, F44322 Nantes 44000, France.
authors.forename: C
authors.initials: C
authors.lastname: Huchet
authors.affiliation: INSERM UMR1087/ CNRS UMR6291, Institut du Thorax, Therassay, Université de Nantes, Faculté des Sciences et des Techniques, F44322 Nantes 44000, France.
authors.forename: A
authors.initials: A
authors.lastname: Lafoux
authors.affiliation: Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, 75724 cedex15, Paris, France.|Service de réanimation médico-chirurgicale adulte, Hôpital Raymond Poincaré, Garches 92380, France.|Université Versailles Saint Quentin, Versailles 78000, France.|TRIGGERSEP, F-CRIN Network, Versailles 78000, France.
authors.forename: T
authors.initials: T
authors.lastname: Sharshar
authors.affiliation: Department of Developmental and Stem Cell Biology, Institut Pasteur, Stem Cells and Development, 75724 cedex15, Paris, France.|Team Stability of Nuclear and Mitochondrial DNA, CNRS UMR 3525, 75724 cedex15, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Ricchetti
authors.affiliation: Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, 75724 cedex15, 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.
authors.forename: F
authors.initials: F
authors.lastname: Chrétien
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008822:Mice, Transgenic; D008931:Mitochondria, Muscle / Q000378:metabolism*; D010538:Peritonitis / Q000150:complications; D017382:Reactive Oxygen Species / Q000378:metabolism; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000473:pathology*; D018805:Sepsis / Q000150:complications* / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species