列纳利多米德和波马利多米德在MSC的存在下调节造血细胞扩张和分化
Sumie Fujii1,2, Yasuo Miura3,4
1Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, 606-8507, Japan. sumief@kuhp.kyoto-u.ac.jp.
International journal of hematology
|July 12, 2024
概括
列纳利多米德和波马利多米德抑制了造血干细胞/原始细胞的成熟,增加了不成熟的细胞. 骨髓中细胞 (MSCs) 保护这些细胞,同时阻碍它们的分化,导致药物诱导的细胞衰减.
科学领域:
- 血液学 血液学 血液学
- 干细胞生物学 干细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 细胞衰竭是莱纳利多米德和波马利多米德治疗血液性恶性瘤的已知并发症.
- 骨髓微环境的作用,特别是介质细胞/干细胞 (MSCs),在调解这种效果方面尚未完全理解.
研究的目的:
- 调查莱纳利多米德和波马利多米德对人类造血干细胞/原始细胞 (HSPC) 的扩张和分化的影响.
- 阐明MSCs在调解这些药物对HSPCs影响中的作用.
主要方法:
- 人类CD34+HSPCs与人类骨髓MSCs的共同培养.
- 用莱纳利多米德和/或波马利多米德治疗.
- 流细胞测量分析以评估HSPC群体 (CD34+,CD38-,CD38+) 和血统差异化 (骨髓,大细胞,红细胞).
- 用花细胞殖民地刺激因子 (G-CSF) 进行骨髓细胞分化试验.
主要成果:
- 列纳利多米德/波马利多米德治疗增加了未成熟的CD34+CD38-HSPCs的比例,同时减少了成熟的CD34+CD38+细胞,表明成熟受阻.
- 这种对成熟的抑制作用在髓状细胞,大核细胞和红色细胞系中观察到.
- MSCs发挥了双重作用:保存不成熟的祖先并抑制它们的分化.
- 在骨髓分化中,列纳利多米德/波马利多米德促进了表达成熟骨髓标记物 (例如CD11b) 的CD34+细胞,但减少了缺乏CD34但表达这些标记物的细胞.
结论:
- 列纳利多米德和波马利多米德抑制HSPC早期成熟,MSCs有助于不成熟的祖先的积累.
- 这些发现为药物诱导的细胞衰减提供了新的机制性见解,并可能为减轻这种不良影响的策略提供信息.
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