克罗恩病的hUC-MSCs疗法:在老鼠TNBS诱导的大肠炎中的疗效和试点临床研究
Qinjuan Sun1, Shan Li1, Ritian Lin1
1Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
EBioMedicine
|April 23, 2024
概括
人类带衍生中介质干细胞 (hUC-MSCs) 在治疗克罗恩病 (CD) 中显示出潜力. 这项试点研究发现,hUC-MSCs在没有严重不良事件的CD患者中改善了愈和减少了炎症.
科学领域:
- 再生医学是一种再生医学.
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
背景情况:
- 介质细胞干细胞 (MSCs),特别是人类带衍生MSCs (hUC-MSCs),是克罗恩病 (CD) 的有希望的治疗方法.
- 在CD中,hUC-MSCs在促进光道愈合的有效性之前没有被研究过.
研究的目的:
- 评估hUC-MSCs在治疗耐火或不适合克罗恩病的患者中的疗效和安全性.
- 研究hUC-MSCs在调节炎症和促进肠道屏障完整性的潜在机制.
主要方法:
- 使用TNBS诱导的大肠炎大鼠模型来评估hUC-MSCs的疗效.
- 17名CD患者通过下注射和静脉滴液接受hUC-MSC,随后进行24周的随访.
- 在体外研究中,与粘膜样本和M1巨细胞共同培养hUC-MSC,以使用RT-PCR和RNA测序分析与炎症和肠道屏障功能相关的基因表达.
主要成果:
- 在CD患者中,hUC-MSCs治疗改善了临床和内镜结果,其中47%的患者表现出内镜反应,17.65%的患者实现了粘膜愈合.
- RNA测序揭示了hUC-MSCs治疗上调肠上皮质屏障完整性基因和下调炎症通路 (TNF,IL-17,TLR信号传递).
- hUC-MSCs减弱了M1巨分化,并抑制了JAK/STAT1酸化,减少了关键的炎症标志物 (IL-1β,IL-6,TNFα).
结论:
- 在大鼠模型中,hUC-MSCs移植证明了缓解大肠炎的有效性.
- 这项试点研究表明hUC-MSCs的使用是耐火性CD患者的潜在有效和安全方法.
- 这些发现为克罗恩病管理的改善结果提供了希望,没有观察到严重的不良事件.
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