循环拉伸增强了来自人类多能干细胞在二维培养中的肝芽阶段的血管新生信号
Koki Yoshimoto1,2,3, Koichiro Maki2,3, Taiji Adachi2,3
1Institute for Integrated Cell-Material Sciences, Institute for Advanced Study, Kyoto University, Kyoto, Japan.
Tissue engineering. Part A
|December 8, 2023
概括
机械刺激,如循环拉伸,可以促进肝发育中的重要血管蛋白信号. 这一发现通过理解关键的细胞间通信信号,推进了用于移植的工程肝脏组织.
科学领域:
- 发展生物学 发展生物学
- 生物工程是生物工程.
- 干细胞生物学 干细胞生物学
背景情况:
- 血管神经信号对于器官发育至关重要,特别是肝脏血管化.
- 人类多能干细胞 (hPSC) 衍生的肝脏器官缺乏透气性,阻碍了肝脏发育研究和移植应用.
- 了解肝芽细胞 (KDR和KDR+细胞) 中的血管新生信号诱导是至关重要的.
研究的目的:
- 研究机械刺激的作用,特别是循环机械拉伸 (cMS),在肝芽阶段促进血管新生信号的作用.
- 开发一个器官在芯片平台,模拟hPSC衍生肝芽的体内机械环境.
- 评估cMS对KDR和KDR+细胞以及随后的肝细胞成熟的影响.
主要方法:
- 利用器官在芯片平台,对hPSC衍生的KDR和KDR+细胞进行循环机械拉伸 (cMS).
- 进行RNA测序以分析基因表达变化,重点关注表皮细胞到介质细胞的过渡和血管神经信号通路.
- 量化了关键血管新生因子 (HGF,MMP9) 的表达和分泌,并评估了肝细胞功能 (CYP3A活性,标记物表达).
主要成果:
- 在共培养的KDR和KDR+细胞中,cMS显著增加了表皮细胞转移基因和血管性信号 (HGF,MMP9) 的表达.
- 在共同培养中,cMS显著增强了HGF和MMP9的表达和分泌,但在单一培养中却没有.
- 与对照组相比,与cMS成熟的肝细胞表现出维持的肝细胞标志物表达和显著更高的CYP3A活性.
结论:
- 循环机械拉伸是诱导肝芽阶段血管新生信号的关键因素.
- 器官芯片模型有效地复制了体内机械条件,以研究肝芽发育.
- 这项研究为改善工程肝脏组织的治疗应用提供了关键的见解.
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