背景:间充质干细胞(MSCs)具有强大的免疫调节能力。本研究旨在评估人脐带间充质干细胞(UMSCs)治疗溃疡性结肠炎(UC)的疗效和安全性,并探讨其可能的机制。
方法:这种前瞻性,自身对照临床研究在河南省人民医院进行。中度至重度活动性UC患者,从2018年9月至2023年3月,对传统药物无反应的研究持续纳入.以1×106/kg的细胞剂量每月静脉内施用UMSC,持续两个月。主要结果是2个月时的临床反应。使用酶联免疫吸附测定试剂盒分析患者血浆中细胞因子和孕激素的水平,纵向数据采用广义估计方程进行分析。
结果:纳入41例患者并接受UMSC治疗。2个月时,73.2%(30/41)的患者达到临床反应,41.5%(17/41)达到临床缓解。6个月时,2例患者失访;相应的数字分别为70.0%(25/41)和34.2%(14/41),分别。UMSC治疗后,梅奥得分,梅奥内镜评分,与基线值相比,溃疡性结肠炎内镜严重程度指数和南希指数的平均值和最大值均显著降低.此外,孕激素和炎症标志物的水平,如白细胞介素(IL)-1β,IL-6,IL-8,IL-12和IL-17A降低,而血红蛋白,白蛋白,IL-10/IL-17A比值增加,特别是在响应组中。多元逐步logistic回归分析显示,年龄是影响疗效的独立危险因素(优势比,0.875(95%置信区间(0.787,0.972));年龄的受试者工作特征曲线下面积为0.79。在UMSC治疗期间或之后未观察到严重不良事件。
结论:UMSCs对UC患者安全有效,年龄是影响疗效的独立危险因素。机械上,UMSC治疗可以改善细胞衰老并抑制促炎细胞因子的分泌。
背景:该研究在www上进行了回顾性注册。chictr.org.cn/(ChiCTR1900026035)于2019年9月18日。
BACKGROUND: Mesenchymal stem cells (MSCs) possess powerful immunomodulatory ability. This study aimed to assess the efficacy and safety of human umbilical cord-derived mesenchymal stem cells (UMSCs) in patients with ulcerative colitis (UC) and to explore the potential mechanisms.
METHODS: This prospective, self-controlled clinical study was conducted at Henan Provincial People\'s Hospital. Patients with moderate-to-severe active UC, unresponsive to traditional drugs were continuously enrolled from September 2018 to March 2023. UMSCs were administered intravenously monthly for two months at a cell dosage of 1 × 106 per kg. The primary outcome was a clinical response at 2 months. The levels of cytokines and progerin in the plasma of the patients were analyzed using enzyme-linked immunosorbent assay kits, and longitudinal data was analyzed using generalized estimation equation.
RESULTS: Forty-one patients were enrolled and received UMSC therapy. At 2 months, 73.2% (30/41) of patients achieved a clinical response, and 41.5% (17/41) achieved a clinical remission. At 6 months, 2 patients were lost to follow-up; the corresponding figures were 70.0% (25/41) and 34.2% (14/41), respectively. After UMSC therapy, the Mayo score, Mayo endoscopy score, mean and maximum values of Ulcerative Colitis Endoscopic Index of Severity and Nancy index were significantly reduced compared with baseline values. Additionally, the levels of progerin and inflammatory markers, such as interleukin (IL)-1β, IL-6, IL-8, IL-12, and IL-17 A decreased, while hemoglobin, albumin, and IL-10/IL-17 A ratio increased, particularly in the response group. Multiple stepwise logistic regression analysis showed age was an independent risk factor affecting efficacy (odds ratio, 0.875 (95% confidence interval (0.787, 0.972)); the area under the receiver operating characteristic curve for age was 0.79. No serious adverse events were observed during or after UMSC therapy.
CONCLUSIONS: UMSCs are safe and effective for patients with UC, with age being an independent risk factor affecting efficacy. Mechanistically, UMSC treatment may ameliorate cell senescence and suppress the secretion of pro-inflammatory cytokines.
BACKGROUND: The study was retrospectively registered at www.chictr.org.cn/ (ChiCTR1900026035) on September 18, 2019.