Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
Tissue Eng Part C Methods. 2021 Jun;27(6):378-390. doi: 10.1089/ten.TEC.2020.0365.
Idiopathic pulmonary fibrosis (IPF) is a severe health problem characterized by progressive fibroblast proliferation and aberrant vascular remodeling. However, the lack of a suitable 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 IPF-3D model using human lung fibroblasts and microvascular endothelial cells. We fabricated an 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 IPF-3D model showed drug responsiveness to two antifibrosis drugs that have recently been approved worldwide. This 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. Impact statement We established a novel model mimicking idiopathic pulmonary fibrosis. Three-dimensional culture was constructed by layer-by-layer cell coating technique. This novel model provides a visualization of fibroblast-specific function. This assay allows for the assessment of pulmonary microvascular environment. Our model may be useful for predicting the efficacy of novel antifibrosis drugs.
特发性肺纤维化（IPF）是一种严重的健康问题，其特征是成纤维细胞增殖和异常血管重塑。然而，缺乏能够复制 IPF 组织中细胞特异性变化的合适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，有助于开发新型抗纤维化药物。我们已经建立了一种逐层（LbL）细胞涂层技术，能够构建 3D 组织和血管化的 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 IPF-3D 模型。我们使用 LbL 细胞涂层技术制造了一个 IPF-3D 模型，以提供源自 IPF 的成纤维细胞的特异性功能和异常微血管结构。我们还发现，这种 IPF-3D 模型对两种最近在全球范围内获得批准的抗纤维化药物具有药物反应性。这种由 LbL 细胞涂层技术构建的 IPF-3D 模型有助于理解 IPF 中成纤维细胞的功能和微血管环境，也可用于预测新型抗纤维化药物的疗效。
我们建立了一种模拟特发性肺纤维化的新型模型。通过逐层细胞涂层技术构建了 3D 培养。这种新型模型提供了对成纤维细胞特异性功能的可视化。该测定法允许评估肺微血管环境。我们的模型可能有助于预测新型抗纤维化药物的疗效。
