永生化介质干细胞 过度表达α-1抗素 保护阿基纳细胞免受阿波和费罗细胞死亡
Sara Shoeibi1, Erica Green1, Hua Wei1
1MUSC.
Research square
|August 23, 2023
概括
不朽化的干细胞通过抑制亡和铁亡来防止胰腺炎诱导的细胞死亡. 这些发现支持用于慢性胰腺炎治疗的干细胞疗法.
科学领域:
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
- 再生医学是一种再生医学.
背景情况:
- 慢性胰腺炎 (CP) 涉及炎症和功能障碍.
- 初级介质干细胞/干细胞 (MSCs) 具有治疗潜力,但经历衰老.
- 永生化MSCs (iMSCs) 为克服衰老限制提供了一个潜在的解决方案.
研究的目的:
- 为了产生和表征不朽的人类MSCs (iMSCs) 和α-1抗素过度表达MSCs (iAAT-MSCs).
- 评估iMSCs和iAAT-MSCs在体外对2,4,6-Trinitrobenzenesulfonic acid (TNBS) 诱导的细胞死亡的保护作用.
- 研究涉及亡和铁亡的潜在机制.
主要方法:
- 使用猿类病毒40大T抗原 (SV40LT) 进行初级MSCs的不朽化.
- 对iMSC和iAAT-MSC线路的表征,以扩散,衰老,表型和差异化.
- 评估TNBS诱导的亡,铁亡,ER压力,线粒体功能和结完整性在培系统中.
主要成果:
- iMSCs和iAAT-MSCs抑制了TNBS诱导的早期亡,并减少了ER压力.
- 这些细胞保留了紧密结合蛋白,调节了线粒体呼吸,ATP含量和ROS产生.
- 通过调节FTH1/PDI/GPX4通路和调节ROS和铁代谢,iMSCs和iAAT-MSCs改善了铁亡.
结论:
- 铁亡被确定为TNBS诱导的细胞死亡的关键机制.
- 不朽化MSCs显示显著的保护作用,防止CP相关的细胞损伤.
- 这些发现为慢性胰腺炎的干细胞治疗提供了机械洞察力.
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