BIOFABICS, Rua Alfredo Allen 455, Porto, 4200-135, Portugal.
Department of Bioprocessing and Bioanalytics, Fraunhofer Institute for Biomedical Engineering IBMT, Joseph-von-Fraunhofer-Weg 1, 66280, Sulzbach, Germany.
Adv Biol (Weinh). 2022 Feb;6(2):e2101139. doi: 10.1002/adbi.202101139. Epub 2021 Dec 27.
The substantial socioeconomic burden of lung diseases, recently highlighted by the disastrous impact of the coronavirus disease 2019 (COVID-19) pandemic, accentuates the need for interventive treatments capable of decelerating disease progression, limiting organ damage, and contributing to a functional tissue recovery. However, this is hampered by the lack of accurate human lung research models, which currently fail to reproduce the human pulmonary architecture and biochemical environment. Induced pluripotent stem cells (iPSCs) and organ-on-chip (OOC) technologies possess suitable characteristics for the generation of physiologically relevant in vitro lung models, allowing for developmental studies, disease modeling, and toxicological screening. Importantly, these platforms represent potential alternatives for animal testing, according to the 3Rs (replace, reduce, refine) principle, and hold promise for the identification and approval of new chemicals under the European REACH (registration, evaluation, authorization and restriction of chemicals) framework. As such, this review aims to summarize recent progress made in human iPSC- and OOC-based in vitro lung models. A general overview of the present applications of in vitro lung models is presented, followed by a summary of currently used protocols to generate different lung cell types from iPSCs. Lastly, recently developed iPSC-based lung models are discussed.
肺部疾病带来了巨大的社会经济负担，最近 2019 年冠状病毒病（COVID-19）大流行的灾难性影响更加凸显了需要有能够减缓疾病进展、限制器官损伤并有助于功能组织恢复的干预性治疗方法。然而，这受到缺乏准确的人类肺部研究模型的阻碍，这些模型目前无法复制人类肺部结构和生化环境。诱导多能干细胞（iPSC）和器官芯片（OOC）技术具有生成生理相关的体外肺模型的合适特征，可用于发育研究、疾病建模和毒理学筛选。重要的是，根据 3R（替代、减少、优化）原则，这些平台代表了动物测试的潜在替代品，并有望根据欧洲 REACH（化学品注册、评估、授权和限制）框架识别和批准新的化学品。因此，本综述旨在总结基于人诱导多能干细胞和器官芯片的体外肺模型的最新进展。本文首先概述了体外肺模型的当前应用，然后总结了目前用于从 iPSC 生成不同肺细胞类型的方案。最后，讨论了最近开发的基于 iPSC 的肺模型。
