高通量生物打印3D培养,用于在生物启发的微环境中探测宿主-病原体相互作用.
Jodi Graf1, DeVonte Moore2, Catherine L Grimes2,3
1Chemical and Biomolecular Engineering, University of Delaware Newark DE USA cfromen@udel.edu akloxin@udel.edu.
概括
这项研究开发了一种高通量3D培养模型,用于研究免疫细胞对病原体的反应. 该模型表明,肺组织的度会影响巨细胞的行为和细菌感染的结果.
科学领域:
- 生物技术是生物技术.
- 免疫学 免疫学 免疫学
- 生物材料科学 生物材料科学
背景情况:
- 免疫细胞的微环境对免疫细胞的功能和命运进行了关键调节.
- 三维 (3D) 培养系统为组织模拟环境中的免疫反应提供了洞察力.
- 当前的3D模型往往缺乏高通量能力,阻碍了在宿主-病原体相互作用研究中的广泛应用.
研究的目的:
- 建立一个高吞吐量巨细胞-细菌共同培养模型,模仿肺组织硬度.
- 为了研究不同的微环境度如何影响巨细胞的行为和对细菌感染的反应.
- 为研究宿主-病原体相互作用和开发治疗策略提供一个平台.
主要方法:
- 利用生物打印技术将人类THP-1单细胞封装和分化为合成细胞外基质 (ECM) 内的巨细胞.
- 使用定义的聚合物和生物墨水制造的ECM,采用96孔板格式,以模仿健康 (符合) 和患病 (硬) 肺组织的硬度.
- 评估了巨细胞的活力,免疫能力 (表型,细胞化,对刺激的反应) 和基因表达.
- 在不同的硬度条件下研究了巨细胞对*Pseudomonas aeruginosa*感染的免疫反应.
主要成果:
- 巨细胞在3D培养系统中保持了生存能力和免疫能力.
- 硬化 (纤维化启发) ECM 中的巨体显示出较高的基础表达炎症和纤维化基因,与符合条件的 (健康的肺部启发) ECM 相比.
- 作为对P. aeruginosa*的反应,与符合条件的环境相比,在刚性微环境中的巨体表现出改变的细胞因子分泌 (IL-6/IL-1β减少,IL-10/TNF-α增加) .
结论:
- 开发的高通量3D模型有效地模拟了肺组织的硬性,并允许对宿主-病原体相互作用进行受控研究.
- 微环境的刚性显著影响巨细胞的免疫反应,包括细菌感染期间的基因表达和细胞因子概况.
- 该平台有助于对细菌感染的理解,并有助于确定潜在的治疗策略.
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