TY -的A2奇门蒂Isotta盟——张,小燕盟——杨Yazhi AU -杨,杨AU - Chen Huijun AU - Tu, Huaijun AU -李,剑PY - 2020 DA - 2020/12/14 TI -液从骨髓Microenvironment-Derived间充质干细胞影响CML细胞生长和促进酪氨酸激酶抑制剂的耐药性SP - 8890201六世- 2020 AB -尽管取得了重大进展在治疗慢性粒细胞白血病(CML)通过酪氨酸激酶抑制剂,撤军后患者复发,需要长期药物治疗。这反映了CML克隆还没有完全消除。CML细胞的精确维护机制尚未完全了解。骨髓白血病细胞的微环境构成了避难所。间充质干细胞(MSC)是骨髓微环境的一个重要组成部分(BM)。它扮演着一个重要的角色在CML的发展和耐药性。越来越多的证据表明,液在细胞间的交流起着至关重要的作用。我们成功地分离和纯化液从人类骨髓microenvironment-derived间充质干细胞(hBMMSC-Exo)连续离心。在目前的研究中,我们调查的影响hBMMSC-Exo增殖,凋亡,CML细胞的耐药性。结果表明,hBMMSC-Exo有能力通过miR-15a抑制CML细胞在体外的增殖和逮捕在G0 / G1期细胞周期。 However, the results obtained from BALB/c nu/nu mice studies apparently contradicted the in vitro results. In fact, hBMMSC-Exo increased tumor incidence and promoted tumor growth in vivo. Further study showed the antiapoptotic protein Bcl-2 expression increased, whereas the Caspase3 expression decreased. Moreover, the in vivo study in the xenograft tumor model showed that hBMMSC-Exo promoted the proliferation and decreased the sensitivity of CML cells to tyrosine kinase inhibitors, resulting in drug resistance. These results demonstrated that hBMMSC-Exo supported the maintenance of CML cells and drug resistance in BM by cell-extrinsic protective mechanisms. They also suggested that hBMMSC-Exo might be a potential target to overcome the microenvironment-mediated drug resistance. SN - 1687-966X UR - https://doi.org/10.1155/2020/8890201 DO - 10.1155/2020/8890201 JF - Stem Cells International PB - Hindawi KW - ER -