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

Br J Anaesth. 2018 Dec;121(6):1249-1259. doi: 10.1016/j.bja.2018.03.032. Epub 2018 May 24.


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 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.

Methods: Micro-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.

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.

Keywords: inflammation; mesenchymal stem cell; prostaglandin–endoperoxide synthases; sepsis.

MeSH terms

  • Acute Disease
  • Adipose Tissue / transplantation*
  • Animals
  • Disease Models, Animal
  • Inflammation / prevention & control*
  • Injections
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Sepsis / complications*