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Stem cells:骨髓干细胞壁龛可发生适应性重塑来对抗白血病壁龛

2018-08-06 MedSci MedSci原创

越来越多的研究集中于白血病情况下骨髓(BM)造血干细胞(HSC)壁龛的细胞性质及其退行性改变。但是,壁龛细胞对生理刺激信号变化的动态适应在很大程度上尚未得到证实。Seon‐Yeong Jeong等研究人员采用5-氟尿嘧啶诱导建立一种壁龛刺激模,并利用该模型发现间充质细胞可迅速逆转成为壁龛样基质细胞,表现为血小板衍生生长因子受体α+/leptin受体+(PL)表现。这些细胞选择性诱导壁龛信号分子,J

越来越多的研究集中于白血病情况下骨髓(BM)造血干细胞(HSC)壁龛的细胞性质及其退行性改变。但是,壁龛细胞对生理刺激信号变化的动态适应在很大程度上尚未得到证实。

Seon‐Yeong Jeong等研究人员采用5-氟尿嘧啶诱导建立一种壁龛刺激模,并利用该模型发现间充质细胞可迅速逆转成为壁龛样基质细胞,表现为血小板衍生生长因子受体α+/leptin受体+(PL)表现。这些细胞选择性诱导壁龛信号分子,Jagged-1,而非CXCL12,通过Jagged-1依赖性方式激活刺激诱导的HSCs再生。

间充质细胞逆转成壁龛样细胞的发生不依赖有丝分裂激活。该逆转过程伴随原发性间充质细胞特性的获得,包括快速诱导阶段特异性的胚胎抗原-3和获得克隆性潜能。刺激诱导的BM壁龛重构可正性刺激正常HSC再生,但对白血病细胞表现为抑制作用,使得BM壁龛的正常HSCs受益匪浅,并延长白血病移植瘤模型鼠的存活期。

总而言之,本研究表明BM微环境受刺激时可发生适应性变化,骨髓壁龛可向类正常/抗白血病微环境方向重塑,从而抵消白血病壁龛驱动的侵袭性促白血病变化,进一步推动了抗白血病靶向壁龛疗法的发展。

原始出处:

Seon‐Yeong Jeong,Jin‐A Kim,Il‐Hoan Oh.The Adaptive Remodeling of Stem Cell Niche in Stimulated Bone Marrow Counteracts the Leukemic Niche.Stem cells. July 13,2018.https://doi.org/10.1002/stem.2870

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    2018-11-13 维他命
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