快速调动发现一种高度可移植的造血干细胞
Jonathan Hoggatt1, Pratibha Singh2, Tiffany A Tate3
1Harvard Medical School, Cancer Center and Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA 02129, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Cell
|December 12, 2017
概括
使用GROβ和AMD3100的新型干细胞动员方法快速收集造血干细胞. 与传统的粒细胞殖民地刺激因子 (G-CSF) 疗法相比,这种方法提高了移植质量和移植效率.
科学领域:
- 血液学
- 免疫学
- 药理学
背景情况:
- 血造干细胞移植 (HSCT) 对各种疾病具有治疗潜力.
- 提高干细胞采集效率和移植质量对于改善HSCT结果和扩大供体库至关重要.
研究的目的:
- 开发一个快速高效的干细胞调动疗法.
- 调查快速干细胞调动的机制,并评估移植质量.
主要方法:
- 开发了一种结合CXCR2激动剂 (GROβ) 和CXCR4抗剂 (AMD3100) 的调动疗法.
- 进行单次注射组合剂以评估干细胞动员动力和大小.
- 进行了涉及中性粒细胞信号传递,MMP-9释放和MMP-9遗传多态性分析的机制研究.
- 在临床前模型中评估动员干细胞的移植效率.
主要成果:
- 一次注射GROβ和AMD3100诱导了快速的干细胞调动,在15分钟内达到峰值.
- 调动的程度与标准的多日颗粒细胞殖民地刺激因子 (G-CSF) 疗法相当.
- 调动涉及中性粒细胞的协同信号,导致增强的矩阵金属蛋白酶-9 (MMP-9) 释放.
- 在MMP-9中意外发现影响其活性的基因多态性.
- 通过这种疗法调动的干细胞比G-CSF调动的细胞具有优越的贩运和更高的移植效率.
结论:
- 新的GROβ和AMD3100疗法为造血干细胞动员提供了快速有效的策略.
- 这种方法产生了优质的移植和增强的移植潜力.
- 对MMP-9多态的进一步研究可能为干细胞动员和移植增强提供额外的见解.
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