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- A Bouglé, P Rocheteau, M Hivelin, A Haroche, D Briand, C Tremolada, J Mantz, and F Chrétien.
- Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, Paris, France; Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Anesthe... more
- Br J Anaesth. 2018 Dec 1; 121 (6): 1249-1259.
BackgroundSevere sepsis has a high mortality rate. There is increasing evidence that human mesenchymal stem cells possess immunomodulatory properties in sepsis, particularly those from adipose tissue. We hypothesised that micro-fragmented human fat, obtained with minimal alteration of the stromal vascular niche, attenuates the inflammatory response and improves outcome in a murine model of sepsis.MethodsMicro-fragmented fat, lipoaspirate, or saline was administered intraperitoneally 2 h after caecal ligation and puncture (CLP) in C57Bl/6RJ ketamine-xylazine anaesthetised mice. The primary endpoint was the inflammatory score. Secondary endpoints included survival, physiological, histological, and biological parameters.ResultsIn CLP mice, micro-fragmented fat administration significantly decreased the median (range) inflammatory score compared with saline [17 (14-20) vs 9 (8-12), P=0.006]. Secondary endpoints were also significantly improved in micro-fragmented fat-treated compared with saline-treated CLP mice. Improvement in inflammatory score and in survival was suppressed when micro-fragmented fat was co-administered with liposomes loaded with clodronate (macrophage toxin) or NS-398 (cyclo-oxygenase 2 inhibitor), but not with SC-560 (cyclo-oxygenase 1 inhibitor).ConclusionsIn a murine model of severe sepsis, micro-fragmented fat improved early inflammatory status and outcome, at least in part, by a cyclo-oxygenase-2-mediated mechanism. The potential therapeutic value of micro-fragmented fat in severe sepsis warrants further investigation.Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
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