在对齐的纤维素基质上培养的内皮层表现出增强的屏障完整性
Ju Hae Choi1, Heejeong Yoon1, Tae-Eun Park1
1Dept. of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology (UNIST), 50 UNIST-gil, Eonyang-eup, Ulju-gun, Ulsan, Republic of Korea 44919. jookang@unist.ac.kr.
Lab on a chip
|August 1, 2025
概括
研究人员在微生理系统 (MPS) 中开发了一种对齐纤维素矩阵 (aFM),以改善内皮屏障功能. 与传统方法相比,这种新的方法提高了细胞结合的完整性,并减少了转移性癌细胞的传播.
科学领域:
- 生物材料科学 生物材料科学
- 细胞生物学 细胞生物学
- 微流体学 微流体学
背景情况:
- 血管内皮在细胞和分子运输中起着至关重要的作用.
- 微生理系统 (MPS) 用于模拟药物测试和细胞转移研究的屏障功能.
- 传统的MPS方法使用带有稀疏细胞外基质的多孔膜,导致不成熟的内皮屏障功能.
研究的目的:
- 在MPS中开发一个增强内皮膜屏障完整性的微环境.
- 研究对齐纤维素矩阵 (aFM) 对内皮细胞行为和屏障功能的影响.
- 通过改善内皮壁垒来评估转移性癌细胞传播的调节.
主要方法:
- 在微流体MPS装置中制造一个对齐的纤维素矩阵 (aFM),使用人类血小板贫富的血和聚丝轨道蚀刻膜.
- 人类静脉内皮细胞 (HUVEC) 的培养在aFM,同位素导向纤维素基质 (iFM) 和纤维菌素 (FN) 涂层膜上.
- 评估内皮屏障完整性,连接蛋白表达 (VE-cadherin,紧密连接) 和透性.
- 与转移性人类乳腺癌细胞 (MDA-MB-231) 进行共同培养实验,以评估转移.
主要成果:
- 在aFM培养的HUVEC显示出延长和定向对齐,附着蛋白和紧结蛋白表达量增加了多达2.5倍.
- 与iFM或FN涂层膜相比,aFM上的内皮层具有超过30%的透性.
- 与传统方法相比,基于aFM的内皮壁垒保持了VE-cadherin的完整性,并显著减少了MDA-MB-231细胞传播.
结论:
- 不同类型的细胞外基质 (ECM) 微环境,如aFM,增强内皮屏障的完整性和MPS中的功能.
- 这种方法可以更好地控制细胞转移,特别是转移性癌细胞.
- 开发的MPS平台通过调节机械线索和基因表达来研究屏障功能,提供了一种多功能工具.
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