School of Pharmacy, Jiangsu University, 212013, ZhenJiang, PR China.
School of Pharmacy, Jiangsu University, 212013, ZhenJiang, PR China.
Phytomedicine. 2024 Dec;135:156173. doi: 10.1016/j.phymed.2024.156173. Epub 2024 Oct 22.
Mesenchymal stem cells (MSCs) possess the capability to mitigate multiorgan failure (MOF) and reduce mortality rates in sepsis. However, their survival is significantly limited due to oxidative stress responses triggered by excessive sepsis inflammation. Previous studies have demonstrated that the paracrine effect of MSCs can be enhanced by cytokine stimuli such as IL-1β, TNF-α, and IFN-γ, a process known as inflammatory licensing. This enhancement, however, may potentially lead to the apoptosis of MSCs.
To investigate the therapeutic effects of Fructus Lycii oligosaccharide (FLO)-nasal mucosa-derived ectodermal MSCs (EMSCs) on septic rats and the underlying mechanisms.
FLO was screened from 21 distinct saccharides derived from traditional Chinese medicine (TCM), utilizing macrophage lipid raft chromatography prepared by our laboratory as the primary screening method.. The comparison of EMSCs primed with/without FLO was assessed through RNA-seq. Cecal ligation and puncture (CLP) surgery was performed in the CLP, EMSCs, and FLO-EMSCs groups (n = 10). The NC group underwent cecal ligation without puncture. The therapeutic effects of EMSCs and FLO-EMSCs on septic rats were evaluated through multiple tests including RT-PCR, western blot, histochemical staining, etc. RESULTS: FLO promoted M2 polarization of macrophages and enhanced the paracrine effect of EMSCs, without inducing apoptosis. Furthermore, FLO promoted GSH synthesis in EMSCs, aiding in the removal of reactive oxygen species (ROS) within these cells. The FLO-treated EMSCs demonstrated enhanced protection against pyroptosis in macrophages, thereby preventing immune paralysis during sepsis.
This study presents an innovative approach for enhancing the anti-inflammatory properties of MSCs using a TCM-derived oligosaccharide, thereby improving their therapeutic efficacy in sepsis models.
间充质干细胞（MSCs）具有减轻多器官衰竭（MOF）和降低脓毒症死亡率的能力。然而，由于过度脓毒症炎症引发的氧化应激反应，它们的存活率受到严重限制。先前的研究表明，MSC 的旁分泌效应可以通过细胞因子刺激（如 IL-1β、TNF-α 和 IFN-γ）增强，这一过程称为炎症许可。然而，这种增强可能会导致 MSC 凋亡。
研究枸杞低聚糖（FLO）-鼻黏膜衍生外胚层间充质干细胞（EMSCs）对脓毒症大鼠的治疗作用及其潜在机制。
利用我们实验室制备的巨噬细胞脂筏色谱法，从 21 种不同的中药来源的糖中筛选出 FLO。通过 RNA-seq 比较 FLO 预处理和未预处理的 EMSCs。在 CLP、EMSCs 和 FLO-EMSCs 组（n=10）中进行盲肠结扎和穿刺（CLP）手术。NC 组仅进行盲肠结扎而不穿刺。通过 RT-PCR、western blot、组织化学染色等多项测试评估 EMSCs 和 FLO-EMSCs 对脓毒症大鼠的治疗效果。
FLO 促进巨噬细胞 M2 极化，增强 EMSCs 的旁分泌效应，同时不会诱导细胞凋亡。此外，FLO 促进了 EMSCs 中 GSH 的合成，有助于清除细胞内的活性氧（ROS）。FLO 处理的 EMSCs 对巨噬细胞的焦亡具有更强的保护作用，从而防止脓毒症期间的免疫麻痹。
本研究提出了一种利用中药来源的寡糖增强 MSC 抗炎特性的创新方法，从而提高了它们在脓毒症模型中的治疗效果。
