通过微型图案的细胞封闭诱导癌症相关纤维细胞的表型变化
Aleksandr Mitriashkin1, Josephine Yu Yan Yap2, Elekuttige Anton Kanishka Fernando2
1Translational Tumor Engineering Laboratory, Department of Biomedical Engineering, National University of Singapore, Singapore 119276, Singapore; Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
Acta biomaterialia
|December 5, 2024
概括
控制癌症相关纤维细胞 (CAF) 形态在体外使用微模式影响其表型和药物反应. 这种方法有助于创建强大的CAF状态,用于研究CAF可塑性和开发向疗法.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 生物材料工程 生物材料工程
背景情况:
- 癌症相关纤维细胞 (CAFs) 是瘤微环境中的关键 stromal 细胞,表现出显著的转录组异质性.
- 在体外了解和复制各种CAF表型对于癌症研究至关重要,但由于CAF的可塑性而具有挑战性.
- 目前的体外模型很难重复不同CAF子集的体外复杂性和特定状态.
研究的目的:
- 研究细胞形状和限制在不同硬度的基板上如何影响CAF的转录组形状和表型.
- 为了确定受控形态是否可以在体外诱导特定的CAF状态.
- 评估工程CAF表型对它们对抗癌药物的反应的影响.
主要方法:
- 在聚烯胺水凝上使用微型图案,以精确控制CAF形态和封闭.
- 分析了转录组形状和关键CAF标记物,以应对工程形状和刚度.
- 将微型 CAF 与非微型 CAF 的药物敏感性进行比较.
主要成果:
- 微型 CAF 显示了表型变化,在体内类似于可塑性和炎症性 CAF 的子集.
- 控制细胞形状和限制调节CAF特定标记物和信号通路.
- 与标准培养相比,改造的CAF对抗癌药物的反应不同.
结论:
- 细胞形态和基质特性在体外显著影响CAF表型和转录基因特征.
- 微纹提供了一种产生强大和特定CAF状态的方法,有助于研究CAF可塑性.
- 这种方法对开发以表型为导向的癌症疗法产生影响,这些疗法可以解释CAF异质性和药物反应.
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