Contracting scars from fibrin drops.
Contracting scars from fibrin drops.
复制标题
DOI：
10.1093/intbio/zyac001
复制
发表时间：
2022-02
期刊：
影响因子：
--
通讯作者：
Stephen Robinson;Eric Parigoris;Jonathan Chang;L. Hecker;S. Takayama
中科院分区：
文献类型：
--
作者：
Stephen Robinson;Eric Parigoris;Jonathan Chang;L. Hecker;S. Takayama
本文描述了一种基于纤维蛋白包埋的肺成纤维细胞的微尺度纤维增生和收缩模型，并提供了纤维化的便捷视觉读数。载有细胞的纤维蛋白微凝胶滴是通过水性两相微印刷形成的。细胞沉积胶原蛋白等细胞外基质 (ECM) 分子，而纤维蛋白则逐渐降解。最终，细胞收缩富含胶原蛋白的基质，形成致密的细胞 ECM 球体。球体的大小提供了纤维增生程度的视觉读数。用促纤维化细胞因子 TGF-β1 刺激这种伤口愈合模型会导致过度的疤痕形成反应，表现为胶原蛋白生成增加和细胞 ECM 球体变大。添加药物也改变了疤痕形成情况：FDA 批准的纤维化药物（尼达尼布和吡非尼酮）和 PAI-1 抑制剂 (TM5275) 显着减小了细胞 ECM 球体尺寸。该测定不仅可用于评估抗纤维化药物的效果，而且相对灵敏；少数可以检测亚毫摩尔浓度吡非尼酮效应的体外纤维增生测定之一。尽管本文重点关注肺纤维化，但该方法为研究广泛的纤维化疾病和评估抗纤维化疗法提供了机会。
This paper describes a microscale fibroplasia and contraction model that is based on fibrin-embedded lung fibroblasts and provides a convenient visual readout of fibrosis. Cell-laden fibrin microgel drops are formed by aqueous two-phase microprinting. The cells deposit extracellular matrix (ECM) molecules such as collagen while fibrin is gradually degraded. Ultimately, the cells contract the collagen-rich matrix to form a compact cell-ECM spheroid. The size of the spheroid provides the visual readout of the extent of fibroplasia. Stimulation of this wound-healing model with the profibrotic cytokine TGF-β1 leads to an excessive scar formation response that manifests as increased collagen production and larger cell-ECM spheroids. Addition of drugs also shifted the scarring profile: the FDA-approved fibrosis drugs (nintedanib and pirfenidone) and a PAI-1 inhibitor (TM5275) significantly reduced cell-ECM spheroid size. Not only is the assay useful for evaluation of antifibrotic drug effects, it is relatively sensitive; one of the few in vitro fibroplasia assays that can detect pirfenidone effects at submillimolar concentrations. Although this paper focuses on lung fibrosis, the approach opens opportunities for studying a broad range of fibrotic diseases and for evaluating antifibrotic therapeutics.