通过前列腺素E2进行差异性干细胞和祖细胞贩运
Jonathan Hoggatt1, Khalid S Mohammad, Pratibha Singh
1Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Nature
|March 15, 2013
概括
非类固醇抗炎药物 (NSAIDs) 通过抑制前列腺素E2 (PGE2) 信号传递,促进血造干细胞 (HSC) 从骨髓出. 这增强了HSC移植,为移植提供了治疗策略.
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
- 免疫学 免疫学 免疫学
背景情况:
- 造血干细胞 (HSCs) 需要利基调节,以便终身生产血液.
- 前列腺素E2 (PGE2) 在HSC功能中具有已知的ex vivo作用.
- 骨髓利基内HSCs的体内调节还没有完全理解.
研究的目的:
- 调查内源性前列腺素E2 (PGE2) 在调节骨髓内的造血干细胞 (HSC) 行为的作用.
- 为了确定非类固醇抗炎药物 (NSAID) 治疗是否会影响HSC动员和移植.
- 探索NSAID介导的HSC调动的治疗潜力.
主要方法:
- 在小鼠中进行NSAID治疗以抑制内源性PGE2.
- 从骨髓和外周血液中HSC输出的分析.
- 评估干细胞和祖细胞调动机制.
- 评估血液构造移植的再生能力和长期移植.
- 非人类灵长类动物和人类志愿者的NSAID治疗.
- PGE2受体 (EP4) 淘汰赛小鼠研究.
主要成果:
- 无 NSAID 治疗诱导了来自骨髓的适度 HSC 出口,独立于 SDF-1-CXCR4 轴.
- HSC退出与利基衰减和骨质疏松素水平降低有关.
- 用NSAID动员的造血移植显示出优异的再生能力和移植.
- 在包括人类在内的物种中证实了NSAID介导的退出.
- 减少E-prostanoid 4 (EP4) 受体信号传递,损害了原始细胞的扩张,并促进了干细胞/原始细胞的退出.
结论:
- 内源性PGE2,通过EP4受体发出信号,在骨髓内保留HSC中起着至关重要的作用.
- 无 NSAID 治疗是一种可行的策略,可以动员 HSC 进行增强的治疗移植.
- 这项研究揭示了HSC保留和动员的新型监管机制.
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