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.
Infection and Epidemiology Department, Institut Pasteur Human Histopathology and Animal Models Unit, Paris, France; Centre Hospitalier Sainte-Anne, Service Hospitalo Universitaire, Paris, France.
Br J Anaesth. 2018 Dec;121(6):1249-1259. doi: 10.1016/j.bja.2018.03.032. Epub 2018 May 24.
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.
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.
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).
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.
严重脓毒症的死亡率很高。越来越多的证据表明，人类间充质干细胞在脓毒症中具有免疫调节特性，尤其是来自脂肪组织的间充质干细胞。我们假设，经微小化处理的人体脂肪组织，在基质血管巢最小程度改变的情况下获取，可以减轻炎症反应，并改善脓毒症小鼠模型的预后。
在 C57Bl/6RJ 氯胺酮-甲苯噻嗪麻醉的小鼠盲肠结扎和穿刺（CLP）后 2 小时，通过腹腔内给予微化脂肪、脂肪抽吸物或生理盐水。主要终点是炎症评分。次要终点包括存活、生理、组织学和生物学参数。
在 CLP 小鼠中，与生理盐水相比，微化脂肪给药显著降低了中位数（范围）炎症评分[17（14-20）与 9（8-12），P=0.006]。与生理盐水治疗的 CLP 小鼠相比，微化脂肪治疗的次要终点也显著改善。当微化脂肪与负载有氯膦酸盐（巨噬细胞毒素）或 NS-398（环氧化酶 2 抑制剂）的脂质体或 SC-560（环氧化酶 1 抑制剂）同时给药时，微化脂肪处理的 CLP 小鼠的炎症评分和存活率的改善被抑制，但与环氧化酶 1 抑制剂 SC-560 无关。
在严重脓毒症的小鼠模型中，微化脂肪通过环氧化酶-2 介导的机制改善了早期炎症状态和预后，至少部分如此。微化脂肪在严重脓毒症中的潜在治疗价值值得进一步研究。
