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

A Bouglé; P Rocheteau; M Hivelin; A Haroche; D Briand; C Tremolada; J Mantz; F Chrétien

doi:10.1016/j.bja.2018.03.032

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.

Authors

A Bouglé¹, P Rocheteau², M Hivelin³, A Haroche⁴, D Briand⁴, C Tremolada⁵, J Mantz⁶, F Chrétien⁷

Affiliations

¹ 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 Anesthesiology and Critical Care Medicine, Institute of Cardiology, Pitié-Salpêtrière Hospital, Paris, France.
² Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, Paris, France; Centre Hospitalier Sainte-Anne, Service Hospitalo Universitaire, Paris, France.
³ Department of Plastic Surgery, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (APHP), PRES Sorbonne Paris Cité, Université Paris Descartes, Paris, France.
⁴ Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, Paris, France.
⁵ Istituto Image, Milan, Italy.
⁶ Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, Paris, France; Department of Anesthesiology and Critical Care Medicine, Hôpital Européen Georges-Pompidou, Université Paris-Descartes Sorbonne Paris Cité, France.
⁷ Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, Paris, France; TRIGGERSEP, F-CRIN Network, Versailles, France; Neuropathology Laboratory, Sainte-Anne Hospital, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. Electronic address: fabrice.chretien@pasteur.fr.

PMID: 30442252
DOI: 10.1016/j.bja.2018.03.032

Abstract

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*