诱导炎症的促进剂通过MSCs过度表达免疫抑制因子
Anton Selich1, Jenni Fleischauer1, Tina Roepke2
1Hannover Medical School, Institute of Experimental Hematology, Building J11, HBZ, Level 01, Room, 6540, Hannover, Germany.
Stem cell research & therapy
|September 23, 2023
概括
研究人员为介质细胞 (MSCs) 开发了炎症诱导的促进体,以控制基因表达. 该CXCL11促进剂特别激活了MSC中的IL10分泌,改善了急性肺损伤小鼠模型中的免疫细胞平衡.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物技术是生物技术.
背景情况:
- 介酶体 stromal 细胞 (MSCs) 在炎症驱动疾病中显示出有限的临床成功.
- 目前的策略涉及对构成性免疫抑制的基因修饰,造成感染风险.
- 慢性疾病需要动态的,而不是持续的免疫调节.
研究的目的:
- 在MSC中设计和测试可控转基因表达的炎症诱导促进剂.
- 确定最佳的合成促进剂,并将它们与内源性炎症诱导的基因促进剂进行比较.
- 在急性肺损伤模型中评估IL10作为免疫抑制转基因的有效性.
主要方法:
- 具有转录因子元素和炎症反应动机 (GAS,ISRE) 的合成促进剂.
- 在人类带MSC中集成的促进剂变成了lentiviral载体.
- 通过细胞因子刺激,转录组分析,ELISA和急性肺损伤小鼠模型评估转基因表达.
主要成果:
- 合成促进剂在IFN-γ刺激时表现出高,特定的转基因表达.
- 该CXCL11促进体与多种细胞因子表现出协同活性,表现优于其他细胞因子.
- 工程MSCs (CXCL11-IL10-MSCs) 调节了免疫细胞种群,并在ALI小鼠模型中改善了结果.
结论:
- 开发了一种用于在炎症环境中使用炎症诱导促进剂定制转基因表达的新工具.
- 该CXCL11促进体提供了对MSCs中转基因表达的特定和强有力的控制.
- 这些促进元素在其他炎症状况和细胞类型中具有治疗应用的潜力.
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