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

Pierre Rocheteau (1) , Laurent Chatre (2) , David Briand (1) , M Mebarki (1) , Grégory Jouvion (1) , J Bardon (1) , Clément Crochemore (2) , P Serrani (1) , M Latil (1) , B Matot (3) , Pierre G. Carlier (3, 4) , N Latronico (5) , Corinne Huchet (6) , Aude Lafoux (6) , T Sharshar (7, 8) , Miria Ricchetti (2) , Fabrice Chretien (9, 1, 10)

1 Histopathologie humaine et Modèles animaux
2 Cellules Souches et Développement
3 LRMN - Laboratoire de Résonance Magnétique Nucléaire
4 MIRCEN - Molecular Imaging Research Center [Fontenay-aux-Roses]
5 Anesthesia and Reanimation Department, Department of Surgery
6 ITX - ITX - unité de recherche de l'institut du thorax
7 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
8 Service de réanimation médico-chirurgicale adulte
9 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
10 Laboratoire de Neuropathologie

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.

Mots clés: sepsis; infection; stem-cell; mesenchymal stem cells; satellite cells

Domaines: Interactions cellulaires [q-bio.CB]

Pierre Rocheteau, Laurent Chatre, David Briand, M Mebarki, Grégory Jouvion, et al.. Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy. Nature Communications, 2015, ⟨10.1038/ncomms10145⟩. ⟨pasteur-01246546⟩