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

被引：175

作者：

Rocheteau, P. ^{[1
]}

Chatre, L. ^{[2
,3
]}

Briand, D. ^{[1
]}

Mebarki, M. ^{[1
]}

Jouvion, G. ^{[1
]}

Bardon, J.

Crochemore, C. ^{[2
,3
]}

Serrani, P. ^{[1
]}

Lecci, P. P. ^{[1
]}

Latil, M. ^{[1
]}

Matot, B. ^{[4
,5
]}

Carlier, P. G. ^{[4
,5
]}

Latronico, N. ^{[6
]}

Huchet, C. ^{[7
]}

Lafoux, A. ^{[7
]}

Sharshar, T. ^{[1
,8
,9
,10
]}

Ricchetti, M. ^{[2
,3
]}

Chretien, F. ^{[1
,10
,11
,12
]}

机构：

[1] Inst Pasteur, Human Histopathol & Anim Models Unit, Infect & Epidemiol Dept, F-75724 Paris 15, France

[2] Inst Pasteur, Stem Cells & Dev, Dept Dev & Stem Cell Biol, F-75724 Paris 15, France

[3] CNRS, UMR 3525, Team Stabil Nucl & Mitochondrial DNA, F-75724 Paris 15, France

[4] Inst Myol, NMR Lab, F-75013 Paris, France

[5] CEA, I2BM, MIRCen, NMR Lab, F-75013 Paris, France

[6] Univ Brescia, Dept Surg, Anesthesia & Reanimat Dept, I-25121 Brescia, Italy

[7] Univ Nantes, Fac Sci & Tech, Inst Thorax, INSERM,UMR1087,CNRS,UMR6291, F-44322 Nantes, France

[8] Hop Raymond Poincare, Serv Reanimat Med Chirurg Adulte, F-92380 Garches, France

[9] Univ Versailles St Quentin, F-78000 Versailles, France

[10] TRIGGERSEP, F CRIN Network, F-78000 Versailles, France

[11] Ctr Hosp St Anne, Lab Neuropathol, F-75014 Paris, France

[12] Paris Descartes Univ, Sorbonne Paris Cite, F-75006 Paris, France

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

INTENSIVE-CARE UNIT; SKELETAL-MUSCLE; CRITICAL ILLNESS; SATELLITE CELLS; FUNCTIONAL DISABILITY; OXIDATIVE STRESS; INFLAMMATION; EXPRESSION; GLUTAMINE; REGENERATION;

D O I：

10.1038/ncomms10145

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

共 51 条

[1] Myogenin expression, cell cycle withdrawal, and phenotypic differentiation are temporally separable events that precede cell fusion upon myogenesis [J].