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Blood:移植的造血细胞将线粒体转移给受体间充质干细胞促进骨髓重建

2020-10-13 星云 MedSci原创

造血干/祖细胞(HSPC)的命运受其骨髓(BM)微环境(ME)的严格调控。骨髓移植(BMT)常常需要放射预处理来去除内源性造血细胞。迄今为止,放疗后间质ME是否受损以及如何恢复尚不明确。

造血干/祖细胞(HSPC)的命运受其骨髓(BM)微环境(ME)的严格调控。骨髓移植(BMT)常常需要放射预处理来去除内源性造血细胞。迄今为止,放疗后间质ME是否受损以及如何恢复尚不明确。

放疗后24h和48h,骨髓基质前体细胞的线粒体体积明显减小

该研究发现BM间充质干细胞(MSC)在放疗后其线粒体功能受到严重损害。供体健康的HSPC可将功能性线粒体转移给基质ME,从而改善受体MSC的线粒体活性。

供体造血细胞将线粒体转移给放疗后的受体BM MSC

具体而言,线粒体从健康HSPC向MSC转移依赖于细胞接触,由HSPC连接蛋白43(Cx43)介导。

Cx43缺陷的供体HSPC转移给BM MSC的线粒体减少

造血细胞Cx43缺陷的嵌合小鼠表现出线粒体转移减少,通过在HSPC中的重新表达Cx43或向培养基中加入从Cx43缺陷的HSPC中分离出的线粒体可挽救线粒体转移减少的表现。

AMPK抑制调控线粒体的转移

HSPC细胞内的ATP水平升高激活了嘌呤能受体P2RX7,导致AMPK活性降低,从而显著增加了线粒体向BM MSC的转运。

线粒体转移促进基质细胞增殖和造血恢复

线粒体转移后,宿主基质ME得以恢复,供体HSPC植入增多。Cx43缺失可延缓间充质和成骨细胞的再生,而体内AMPK抑制则可促进间质的恢复。因此,由于支持性基质ME的恢复,造血室的重建也得到了改善。

综上,该研究结果表明,健康供者的HSPC不仅重建了移植后的造血系统,而且通过线粒体转移支持和诱导受体放疗损伤的ME的代谢恢复。了解清髓性应激后基质恢复的调控机制,对于优化骨髓移植程序和强调辅助性、非-HSC在促进造血植入方面的重要性具有重要的临床意义。

原始出处:

Golan Karin,Singh Abhishek K,Kollet Orit et al. Bone marrow regeneration requires mitochondrial transfer from donor Cx43-expressing hematopoietic progenitors to stroma.Blood. September 14,2020.

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    2020-10-16 独孤立克

    干细胞是热点,但是进入临床仍然需要时间和临床疗效验证哦

    0

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    2020-10-15 俅侠
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