低剂量甲德对循环和休息的人类造血干细胞和祖细胞有不同的影响
Maximilien Lora1, H A Ménard2, Anastasia Nijnik3
1The Research Institute of the McGill University Health Centre (RI-MUHC), Montreal, Canada.
Clinical and translational science
|April 28, 2025
概括
低剂量甲状腺素 (LD-MTX) 影响造血干细胞和原生细胞 (HSPC). 在循环的HSPC中,LD-MTX减少了扩散,同时在非循环的HSPC中保持了克隆性.
科学领域:
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
- 药理学 药理学是指药理学的学科.
背景情况:
- 低剂量甲状腺素 (LD-MTX) 是对类风湿性关节炎 (RA) 的主要治疗方法.
- 炎症会影响造血干细胞和原生细胞 (HSPC) 的行为.
- LD-MTX对HSPC的影响尚不清楚.
研究的目的:
- 调查LD-MTX对HSPC的影响.
- 描述LD-MTX吸收及其对HSPC功能的影响.
主要方法:
- 从健康的捐赠者中分离出的CD34+HSPCs.
- 用LD-MTX治疗的HSPC.
- 通过流式细胞计量评估活力,细胞周期,增殖,ROS,DNA损伤和p38激活.
- 使用殖民地形成细胞试验评估HSPC克隆原性.
主要成果:
- 循环HSPCs显示增加减少叶酸载体1 (RFC1) 和更高的细胞内MTX积累.
- LD-MTX诱导了S相停止,增加了ROS和DNA损伤,并在循环HSPC中降低了生存能力.
- 效应由p38 MAPK激活介导,由叶酸逆转,对CD34+CD38High原始体的影响更大.
- 非循环的HSPC表现出减少的增殖,但保持了克隆性.
结论:
- 根据HSPC的自行车状态,HSPC根据不同的情况吸收LD-MTX.
- LD-MTX调节HSPC的增殖和活力,对RA治疗和血液形成有影响.
- 叶酸可以拯救HSPC中的LD-MTX诱导的毒性.
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