原发性肺纤维化（IPF）是一种进行性间质性疾病，其特点是细胞增殖和分化增加，伴随细胞外基质（ECM）沉积过多导致瘢痕组织（纤维化）和肺部重塑。激活和分化的（肌）成纤维细胞是IPF组织重塑的主要来源之一，其与异常或受伤肺上皮之间存在异常交流被公认为一个关键机制，用于解释这一特征。这种上皮-成纤维细胞相互作用模拟了在肺部发育期间被称为上皮间充质营养单元（EMTU）的内胚层和中胚层之间的时间、空间和细胞类型特异性的交流，被认为在健康的肺部修复过程中被激活并在各种肺部疾病，包括IPF中发生了失调。为了研究IPF中失调的肺EMTU，已经建立了多种复杂的离体模型。因此，在本综述中，我们将概述已经使用复杂（三维）离体共培养和器官样病变模型的研究，以评估肺EMTU中异常上皮-成纤维细胞相互作用如何影响IPF的关键特征，包括细胞分化、增殖和迁移的缺陷以及ECM沉积增加。版权所有© 2023国际分化学会。由Elsevier B.V.出版。保留所有权利。

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial disease that is characterized by increased cellular proliferation and differentiation together with excessive extracellular matrix (ECM) deposition leading to buildup of scar tissue (fibrosis) and remodeling in the lungs. The activated and differentiated (myo)fibroblasts are one of the main sources of tissue remodeling in IPF and a crucial mechanism known to contribute to this feature is an aberrant crosstalk between pulmonary fibroblasts and the abnormal or injured pulmonary epithelium. This epithelial-fibroblast interaction mimics the temporal, spatial and cell-type specific crosstalk between the endoderm and mesoderm in the so-called epithelial-mesenchymal trophic unit (EMTU) during lung development that is proposed to be activated in healthy lung repair and dysregulated in various lung diseases including IPF. To study the dysregulated lung EMTU in IPF, various complex in vitro models have been established. Hence, in this review, we will provide a summary of studies that have used complex (3-dimensional) in vitro co-culture, and organoid models to assess how abnormal epithelial-fibroblast interactions in lung EMTU contribute to crucial features of the IPF including defective cellular differentiation, proliferation and migration as well as increased ECM deposition.Copyright © 2023 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.