几何控制的WNT激活驱动肠道形态发生
Nathaniel C Burmas1, Arlyn M Fabian2, Amoli Vanavadiya1
1Department of Chemical and Biomolecular Engineering, Irvine, CA, 92697, USA.
Advanced healthcare materials
|June 23, 2025
概括
工程微环境和WNT信号调制促进肠表皮形态发生. 机械和建筑线索独立地驱动组织形成,提供新的肠模仿培养策略.
科学领域:
- 生物医学工程 生物医学工程
- 细胞生物学 细胞生物学
- 组织工程是组织工程.
背景情况:
- 形态发生结合了生化,机械和建筑线索来形成组织.
- 结肠直肠癌 (Caco-2) 细胞作为研究肠道上皮细胞发育的模型.
研究的目的:
- 为了研究WNT信号调制和工程微环境对Caco-2细胞的密室状形态发生的协同效应.
- 阐明机械和建筑因素在编排肠上皮层形态发生过程中的独立作用.
主要方法:
- 利用纤维细胞条件介质和WNT激动剂 (CHIR) 来调节WNT信号传递.
- 采用数字光处理 (DLP) 打印来制造用于受控微环境的凝甲基酸盐 (GelMA) 微波阵列.
- 评估了上皮细胞芽和粘蛋白2 (MUC2) 表达.
- 破坏了髓的收缩性,以评估机械传导.
主要成果:
- 纤维细胞受条件介质诱导了WNT依赖的上皮质芽,由CHIR增强.
- 经过工程设计的GelMA微,增加了脚手架周边与面积的比率,促进了芽和MUC2上调.
- 机械线索,特别是肌缩性,对于这些形态遗传效应至关重要.
结论:
- 温特信号传输和工程微环境协同驱动了类似密室维卢斯的形态发生.
- 机械和建筑线索可以独立编排肠上皮质形态发生.
- 这些发现为开发肠道模仿培养系统提供了新的策略.
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