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开发一种新的空气-液体接口气道组织等价模型,用于体外呼吸模式研究

Timothy Leach^1,2, Uma Gandhi¹, Kimberly D Reeves³

¹Wake Forest School of Medicine, Medical Center, Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA.

Scientific reports

|June 22, 2023

概括

研究人员使用本地纤维细胞和肺细胞外基质 (ECM) 开发了一种3D气道器官组织等价 (OTE) 模型. 这种先进的模型准确地复制了人类呼吸道的微环境,用于研究肺部生物学和疾病.

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
呼吸系统医学呼吸系统医学

背景情况:

人类呼吸道生物学涉及细胞,细胞外基质 (ECM) 和生物机械微环境之间的复杂相互作用.
现有的体外培养系统往往无法完全复制这些复杂的相互作用,从而限制了它们在研究呼吸道疾病方面的实用性.

研究的目的:

开发和描述一个生理相关的3D空气液体接口 (ALI) 气道器官组织等价 (OTE) 模型.
将原生肺纤维细胞,溶解的肺ECM和可调节的水凝基质纳入OTE模型.
评估这些新型特征对人类支气管上皮 (HBE) 细胞表型和呼吸道屏障功能的影响.

主要方法:

开发一个3D气道OTE模型,包括本地肺纤维细胞,溶解的肺ECM和具有可调节性质的水凝基质.
在空气液体接口 (ALI) 上培养OTE模型28天.
使用跨上皮电阻 (TEER) 和通过多谱免疫组织化学和下一代测序来评估上皮屏障功能和上皮表型.

主要成果:

具有溶解肺ECM和本地肺纤维细胞的OTE培养物显示出差异化良好的ALI培养物.
这些培养物保持了屏障功能,并表达了葡萄杯,俱乐部和状细胞的成熟表皮标记物.
调节水凝刚度并没有阻碍HBE的分化,并且提供了一个改变表皮表型的变量.

结论:

开发的3D气道OTE模型成功地复制了人类气道微环境的关键组件.
该模型为研究正常和病态气道生物学提供了一个多功能和生理相关的平台.
结合原生纤维细胞,肺ECM和可调节的水凝,提高了体外气道模型的准确性.

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