Department of Anorectal Surgery, The Second Hospital of Tianjin Medical University, Tianjin, China.
Department of Laboratory, The Second Hospital of Tianjin Medical University, Tianjin, China.
Int Immunopharmacol. 2024 May 30;133:112092. doi: 10.1016/j.intimp.2024.112092. Epub 2024 Apr 15.
Endometrial regenerative cells (ERCs) have been proven to be an effective strategy for attenuating experimental colitis, but the complex in vivo microenvironment such as oxidative stress may largely limit and weaken ERC efficacy. Melatonin (MT) works as an anti-oxidative agent in a variety of preclinical diseases, and has been identified to promote mesenchymal stem cell-mediated therapeutic effects in different diseases. However, the ability of MT to enhance ERC-mediated effects in colitis is currently poorly understood.
Menstrual blood was collected from healthy female volunteers to obtain ERCs and identified. In vitro, HO-induced oxidative stress was introduced to test if MT could prevent ERCs from damage through detection of intracellular reactive oxidative species (ROS) and apoptosis assay. In vivo, dextran sodium sulfate (DSS)-induced acute colitis was treated by ERCs and MT-primed ERCs, therapeutic effects were assayed by the disease activity index (DAI), histological features, and macrophage and CD4 T cell in the spleen and colon, and cytokine profiles in the sera and colon were also measured.
In vitro, ERCs that underwent MT-precondition were found to possess more anti-oxidative potency in comparison to naïve ERCs, which were characterized by decreased apoptosis rate and intracellular ROS under HO stimulation. In vivo, MT pretreatment can significantly enhance the therapeutic effects of ERCs in the attenuation of experimental colitis, including decreased DAI index and damage score. In addition, MT pretreatment was found to promote ERC-mediated inhibition of Th1, Th17, and M1 macrophage and pro-inflammatory cytokines, increase of Treg, and immunomodulation of cytokines in the spleen and colon.
MT pretreatment facilitates the promotion of cell viability under oxidative stress in vitro, while also enhancing ERC-mediated therapeutic effects in experimental colitis.
子宫内膜再生细胞（ERCs）已被证明是减轻实验性结肠炎的有效策略，但复杂的体内微环境，如氧化应激，可能在很大程度上限制和削弱 ERC 的疗效。褪黑素（MT）在多种临床前疾病中作为抗氧化剂发挥作用，并且已被确定可促进间充质干细胞在不同疾病中的治疗效果。然而，MT 增强 ERC 在结肠炎中介导作用的能力目前知之甚少。
从健康女性志愿者的月经血中采集 ERCs 并进行鉴定。在体外，引入 HO 诱导的氧化应激，通过检测细胞内活性氧（ROS）和细胞凋亡试验，测试 MT 是否可以防止 ERC 受损。在体内，用 ERCs 和 MT 预激活的 ERCs 治疗葡聚糖硫酸钠（DSS）诱导的急性结肠炎，通过疾病活动指数（DAI）、组织学特征以及脾和结肠中的巨噬细胞和 CD4 T 细胞，以及血清和结肠中的细胞因子谱来评估治疗效果。
在体外，与未处理的 ERCs 相比，经过 MT 预处理的 ERCs 具有更强的抗氧化能力，其特征是在 HO 刺激下，细胞凋亡率和细胞内 ROS 降低。在体内，MT 预处理可显著增强 ERC 在减轻实验性结肠炎中的治疗效果，包括降低 DAI 指数和损伤评分。此外，MT 预处理被发现可促进 ERC 介导的抑制 Th1、Th17 和 M1 巨噬细胞和促炎细胞因子，增加 Treg，并调节脾和结肠中的细胞因子。
MT 预处理可促进体外氧化应激下细胞活力的提高，同时增强 ERC 在实验性结肠炎中的治疗效果。
