将人体内皮细胞重新编程为血液细胞需要血管诱导
Vladislav M Sandler1, Raphael Lis2, Ying Liu1
1Ansary Stem Cell Institute, Department of Genetic Medicine, and Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York 10065, USA.
Nature
|July 18, 2014
概括
研究人员使用血管利基线索和转录因子将人体内皮细胞重新编程成可移植的造血干细胞. 这种方法绕过多能干细胞,提供了一种新的策略,用于治疗血液疾病与自身移植.
科学领域:
- 干细胞生物学 干细胞生物学
- 血液形成 血液形成 血液形成
- 细胞重编程 细胞重编程
背景情况:
- 为血液疾病治疗产生可移植的造血细胞是具有挑战性的.
- 目前使用多能干细胞的方法导致植入不良.
研究的目的:
- 开发一种方法,将内皮细胞重新编程成可移植的造血细胞,而不需要多能阶段.
- 模仿血管的微环境来实现这种重编程.
主要方法:
- 用FOSB,GFI1,RUNX1和SPI1 (FGRS) 转录因子对内皮细胞进行转导.
- 在无血清的血管利基单层上传播,以诱导血造原生细胞 (MPP) 的发展.
- 评估免疫缺陷小鼠的移植和分化潜力.
主要成果:
- 重编程内皮细胞 (rEC-hMPPs) 获得了多能原始细胞 (MPP) 的特征.
- rEC-hMPPs证明了持久的移植,并在移植后产生髓状和淋巴状后代.
- 条件FGRS表达和血管诱导激活了内源基因,模仿自我更新的MPPs.
结论:
- 血管位在造血细胞特异化中起着至关重要的作用.
- 这种方法使得针对血液疾病的自身造血体移植的工程成为可能.
- 该方法为基于多能干细胞的疗法提供了潜在的替代方案.
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