Micro-fragmented fat injection reduces sepsis-induced acute inflammatory response in a mouse model

Background: Severe 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 microfragmented human fat, obtained with minimal alteration of the stromal vascular niche, attenuates the inflammatory response and improves outcome in a murine model of sepsis. Methods: Micro-fragmented fat, lipoaspirate, or saline was administered intraperitoneally 2 h after caecal ligation and puncture (CLP) in C57B1/6RJ ketamine-xylazine anaesthetised mice. The primary endpoint was the inflammatory score. Secondary endpoints included survival, physiological, histological, and biological parameters. Results: In 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). Conclusions: In 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.