优化培养条件以产生具有结构复杂性和功能性的血管化多系肝脏有机体
Kyun Yoo Chi1, Gyeongmin Kim1, Hyojin Kim1
1Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea.
Biomaterials
|October 24, 2024
概括
研究人员通过调节信号通路开发了复杂的多谱系肝脏有机体 (mLO). 这些先进的有机体更好地模拟肝脏疾病,包括体细胞和非体细胞,以改善体外研究.
科学领域:
- 干细胞生物学 干细胞生物学
- 肝病学 肝病学是一种肝病学.
- 再生医学是一种再生医学.
背景情况:
- 肝脏有机体 (HOs) 缺乏非辅酶细胞,这限制了它们在模拟肝病病原体中的有用性.
- 多谱系肝脏有机体 (mLO) 提供了更全面的体外模型,但在实现结构复杂性和支持多种细胞类型方面面临挑战.
- 优化培养条件对于mLO内的所有细胞类型仍然是一个重大障碍.
研究的目的:
- 建立一种方法,从人类多能干细胞 (hPSCs) 中产生结构复杂和功能成熟的多血统肝脏器官 (mLO).
- 研究信号通路在mLO的发展和差异化中的作用.
- 为了创建一个更准确的体外模型来研究肝脏疾病.
主要方法:
- 从hPSCs获得的囊性肝脏器官 (HOs) 的长期扩张.
- 囊性HO的组装与hPSC衍生的内皮细胞和肝星状细胞样细胞.
- 在mLO组装和分化过程中使用小分子调节cAMP/Wnt/Hippo信号通路.
主要成果:
- 从hPSCs成功生成了长期可扩展的囊性HOs.
- 确定了传统培养条件导致mLOs偏差差异化.
- 证明调节cAMP/Wnt/Hippo通路可以有效地产生具有体和非体细胞的mLO.
- 在mLOs中观察到结构复杂性和功能成熟度,包括血管网络,胆汁分泌极性和对纤维刺激的反应.
结论:
- 调节信号通路对于提高mLO的结构复杂性至关重要.
- 开发的mLO代表了体外肝病研究的一个有前途的先进模型.
- 这种方法克服了传统的HOS和偏差差异化的局限性,使得更好的疾病建模.
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