Zhu Yueniu, Xu Liqun, Collins Jennifer J P, Vadivel Arul, Cyr-Depauw Chanèle, Zhong Shumei, Mense Lars, Möbius Marius A, Thébaud Bernard
1 Department of Pediatric Critical Care Medicine, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine , Shanghai, China .
2 Department of Pediatrics, Children's Hospital of Eastern Ontario and Children's Hospital of Ontario Research Institute (CHEORI) , Ottawa, Ontario, Canada .
Stem Cells Dev. 2017 Jul 15;26(14):1054-1064. doi: 10.1089/scd.2016.0329. Epub 2017 May 17.
Sepsis is the main cause of morbidity and mortality in neonates. Mesenchymal stromal cells (MSCs) are potent immune-modulatory cells. Their effect in neonatal sepsis has never been explored. We hypothesized that human umbilical cord-derived MSCs (hUC-MSCs) improve survival in experimental neonatal sepsis. Sepsis was induced in 3-day-old rats by intravenous injection of Escherichia coli (5 × 10/rat). One hour after infection, rats were treated intravenously with normal saline, hUC-MSCs, or with interferon-γ preconditioned hUC-MSCs (10 cells/kg). Eighteen hours after infection, survival, bacterial counts, lung neutrophil and macrophage influx, phagocytosis and apoptosis of splenocytes plasma, and LL-37 concentration were evaluated. Animals were observed for survival for 72 h after E. coli injection. Treatment with either hUC-MSCs or preconditioned hUC-MSCs significantly increased survival (hUC-MSCs, 81%; preconditioned hUC-MSCs, 89%; saline, 51%; P < 0.05). Both hUC-MSCs and preconditioned hUC-MSCs enhanced bacterial clearance. Lung neutrophil influx was decreased with preconditioned hUC-MSCs. The number of activated macrophages (CD206) in the spleen was increased with hUC-MSCs and preconditioned hUC-MSCs; preconditioned hUC-MSCs increased the phagocytic activity of CD206 macrophages. hUC-MSCs and preconditioned hUC-MSCs decreased splenocyte apoptosis in E. coli infected rats. Finally, LL-37 plasma levels were elevated in neonatal rats treated with hUC-MSCs or preconditioned hUC-MSCs. hUC-MSCs enhance survival and bacterial clearance in experimental neonatal sepsis. hUC-MSCs may be an effective adjunct therapy to reduce neonatal sepsis-related morbidity and mortality.
脓毒症是新生儿发病和死亡的主要原因。间充质基质细胞（MSCs）是强大的免疫调节细胞。其在新生儿脓毒症中的作用从未被探索过。我们假设人脐带间充质干细胞（hUC-MSCs）可提高实验性新生儿脓毒症的存活率。通过静脉注射大肠杆菌（5×10⁹/只大鼠）在3日龄大鼠中诱导脓毒症。感染后1小时，大鼠静脉注射生理盐水、hUC-MSCs或经干扰素-γ预处理的hUC-MSCs（10⁶个细胞/千克）。感染后18小时，评估存活率、细菌计数、肺中性粒细胞和巨噬细胞浸润、脾细胞吞噬作用和凋亡、血浆以及LL-37浓度。在注射大肠杆菌后观察动物72小时的存活情况。用hUC-MSCs或预处理的hUC-MSCs治疗均显著提高了存活率（hUC-MSCs组为81%；预处理的hUC-MSCs组为89%；生理盐水组为51%；P<0.05）。hUC-MSCs和预处理的hUC-MSCs均增强了细菌清除。预处理的hUC-MSCs使肺中性粒细胞浸润减少。hUC-MSCs和预处理的hUC-MSCs使脾脏中活化巨噬细胞（CD206）的数量增加；预处理的hUC-MSCs增加了CD206巨噬细胞的吞噬活性。hUC-MSCs和预处理的hUC-MSCs减少了大肠杆菌感染大鼠的脾细胞凋亡。最后，用hUC-MSCs或预处理的hUC-MSCs治疗的新生大鼠血浆中LL-37水平升高。hUC-MSCs可提高实验性新生儿脓毒症的存活率并增强细菌清除。hUC-MSCs可能是一种有效的辅助治疗方法，可降低新生儿脓毒症相关的发病率和死亡率。
