ハシモト　カズキ   Kazuki Hashimoto   橋本　一輝    所属   医学部 医学科（附属八千代医療センター）    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Mesenchymal stem cell-derived exosomes for treatment of sepsis.
掲載誌名	正式名：Frontiers in immunology 略　 称：Front Immunol ISSNコード：16643224/16643224
掲載区分	国外
巻・号・頁	14,pp.1136964
著者・共著者	Homma Kento, Bazhanov Nikolay, Hashimoto Kazuki, Shimizu Masaru, Heathman Thomas, Hao Qi, Nawgiri Ranjana, Muthukumarana Vidarshi, Lee Jae Woo, Prough Donald S, Enkhbaatar Perenlei
担当区分	2nd著者
発行年月	2023
概要	INTRODUCTION:The pathogenesis of sepsis is an imbalance between pro-inflammatory and anti-inflammatory responses. At the onset of sepsis, the lungs are severely affected, and the injury progresses to acute respiratory distress syndrome (ARDS), with a mortality rate of up to 40%. Currently, there is no effective treatment for sepsis. Cellular therapies using mesenchymal stem cells (MSCs) have been initiated in clinical trials for both ARDS and sepsis based on a wealth of pre-clinical data. However, there remains concern that MSCs may pose a tumor risk when administered to patients. Recent pre-clinical studies have demonstrated the beneficial effects of MSC-derived extracellular vesicles (EVs) for the treatment of acute lung injury (ALI) and sepsis.METHODS:After recovery of initial surgical preparation, pneumonia/sepsis was induced in 14 adult female sheep by the instillation of Pseudomonas aeruginosa (~1.0×1011 CFU) into the lungs by bronchoscope under anesthesia and analgesia. After the injury, sheep were mechanically ventilated and continuously monitored for 24 h in a conscious state in an ICU setting. After the injury, sheep were randomly allocated into two groups: Control, septic sheep treated with vehicle, n=7; and Treatment, septic sheep treated with MSC-EVs, n=7. MSC-EVs infusions (4ml) were given intravenously one hour after the injury.RESULTS:The infusion of MSCs-EVs was well tolerated without adverse events. PaO2/FiO2 ratio in the treatment group tended to be higher than the control from 6 to 21 h after the lung injury, with no significant differences between the groups. No significant differences were found between the two groups in other pulmonary functions. Although vasopressor requirement in the treatment group tended to be lower than in the control, the net fluid balance was similarly increased in both groups as the severity of sepsis progressed. The variables reflecting microvascular hyperpermeability were comparable in both groups.CONCLUSION:We have
DOI	10.3389/fimmu.2023.1136964
PMID	37180159