通过减轻氧气冲击来提高造血干细胞移植的效率
Charlie R Mantel1, Heather A O'Leary1, Brahmananda R Chitteti2
1Department of Microbiology/Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Cell
|June 16, 2015
概括
在血造干细胞 (HSC) 采集过程中暴露于空气中,会减少长期重新填充的HSCs. 这种外生理氧冲击/压力 (EPHOSS) 现象意味着HSC数量被低估了. 环素A可以保护HSC免受EPHOSS的侵害.
科学领域:
- 血液学 血液学 血液学
- 细胞生物学 细胞生物学
- 干细胞研究 干细胞研究
背景情况:
- 造血干细胞 (HSC) 通常存在于缺氧骨髓和带血中.
- 标准的HSC隔离和处理发生在环境空气中,这是一个非生理条件.
研究的目的:
- 调查环境氧气暴露对HSC恢复的影响.
- 为了确定氧气诱导的HSC损伤背后的机制.
- 探索在细胞采集过程中减轻这种损伤的策略.
主要方法:
- 在本地低氧条件下与周围空气相比,采集和处理骨髓和带血.
- 评估长期重新填充HSC和原生细胞群的评估.
- 对活性氧物种 (ROS) 生产和线粒体透性过渡孔 (MPTP) 诱导的研究.
- 评估MPTP抑制剂环素A的保护作用.
主要成果:
- 短时间暴露于环境氧气显著降低了长期重新填补HSCs的恢复.
- 这种外生理氧冲击/压力 (EPHOSS) 现象导致真正的HSC数量被低估.
- 通过环素D和p53确定ROS的产生和MPTP的诱导是EPHOSS的机制.
- 环素A治疗保护HSC免受EPHOSS,增加了从小鼠骨髓和人类带血液中移植的HSC的恢复.
结论:
- 在采集和加工过程中暴露于环境氧气会导致功能性HSCs的显著损失.
- 了解和减轻EPHOSS对于准确的HSC量化和成功的移植至关重要.
- 药理上抑制MPTP可能为改善HSC移植结果提供临床优势.
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