Idiopathic pulmonary fibrosis (IPF) is a severe health problem characterized by progressive fibroblast proliferation and aberrant vascular remodeling. However, the lack of a suitable in vitro model that replicates cell-specific changes in IPF tissue is a crucial issue. Three-dimensional (3D) cell cultures allow the mimicking of cell-specific functions, facilitating development of novel antifibrosis drugs. We have established a layer-by-layer (LbL) cell coating technique that enables the construction of 3D tissue and also vascularized 3D tissue. This study evaluated whether this technique is beneficial for constructing an in vitro IPF-3D model using human lung fibroblasts and microvascular endothelial cells. We fabricated an in vitro IPF-3D model to provide IPF-derived fibroblasts-specific function and aberrant microvascular structure using the LbL cell coating technique. We also found that this in vitro IPF-3D model showed drug responsiveness to two antifibrosis drugs that have recently been approved worldwide. This in vitro IPF-3D model constructed by a LbL cell coating technique would help in the understanding of fibroblast function and the microvascular environment in IPF and could also be used to predict the efficacy of novel antifibrosis drugs.

中文翻译：

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使用逐层细胞涂层技术的三维特发性肺纤维化模型

特发性肺纤维化 (IPF) 是一种严重的健康问题，其特征是进行性成纤维细胞增殖和异常血管重塑。然而，缺乏在 IPF 组织中复制细胞特异性变化的合适体外模型是一个关键问题。三维 (3D) 细胞培养允许模拟细胞特异性功能，促进新型抗纤维化药物的开发。我们已经建立了一种逐层 (LbL) 细胞涂层技术，可以构建 3D 组织和血管化 3D 组织。本研究评估了该技术是否有利于使用人肺成纤维细胞和微血管内皮细胞构建体外IPF-3D 模型。我们制作了一个体外IPF-3D 模型使用 LbL 细胞涂层技术提供 IPF 衍生的成纤维细胞特异性功能和异常微血管结构。我们还发现，这种体外IPF-3D 模型显示出对最近在全球范围内批准的两种抗纤维化药物的药物反应。这种由 LbL 细胞涂层技术构建的体外IPF-3D 模型将有助于了解 IPF 中的成纤维细胞功能和微血管环境，也可用于预测新型抗纤维化药物的疗效。