Human pluripotent stem cell-derived lung organoids: Potential applications in development and disease modeling.

Q1 Biochemistry, Genetics and Molecular Biology
Lu Tian, Jinghui Gao, Irving M Garcia, Huanhuan Joyce Chen, Alessandra Castaldi, Ya-Wen Chen
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引用次数: 30

Abstract

The pulmonary system is comprised of two main compartments, airways and alveolar space. Their tissue and cellular complexity ensure lung function and protection from external agents, for example, virus. Two-dimensional (2D) in vitro systems and animal models have been largely employed to elucidate the molecular mechanisms underlying human lung development, physiology, and pathogenesis. However, neither of these models accurately recapitulate the human lung environment and cellular crosstalk. More recently, human-derived three-dimensional (3D) models have been generated allowing for a deeper understanding of cell-to-cell communication. However, the availability and accessibility of primary human cell sources from which generate the 2D and 3D models may be limited. In the past few years, protocols have been developed to successfully employ human pluripotent stem cells (hPSCs) and differentiate them toward pulmonary fate in vitro. In the present review, we discuss the advantages and pitfalls of hPSC-derived lung 2D and 3D models, including the main characteristics and potentials for these models and their current and future applications for modeling development and diseases. Lung organoids currently represent the closest model to the human pulmonary system. We further focus on the applications of lung organoids for the study of human diseases such as pulmonary fibrosis, infectious diseases, and lung cancer. Finally, we discuss the present limitations and potential future applications of 3D lung organoids. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cells and Disease Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cell Differentiation and Reversion.

人类多能干细胞衍生的肺类器官:在发育和疾病建模中的潜在应用。
肺系统由两个主要的隔室组成,气道和肺泡空间。它们的组织和细胞的复杂性确保了肺功能和保护免受外部因素(例如病毒)的侵害。二维(2D)体外系统和动物模型已被广泛用于阐明人类肺发育、生理和发病机制的分子机制。然而,这两种模型都不能准确地概括人类肺环境和细胞串扰。最近,人类衍生的三维(3D)模型已经生成,可以更深入地了解细胞间的通信。然而,产生2D和3D模型的原始人类细胞来源的可用性和可及性可能是有限的。在过去的几年中,已经制定了成功地利用人类多能干细胞(hPSCs)并在体外将其分化为肺命运的方案。在这篇综述中,我们讨论了hpsc衍生的肺部2D和3D模型的优点和缺陷,包括这些模型的主要特点和潜力,以及它们在建模开发和疾病方面的当前和未来应用。肺类器官是目前最接近人类肺系统的模型。我们进一步关注肺类器官在肺纤维化、感染性疾病和肺癌等人类疾病研究中的应用。最后,我们讨论了三维肺类器官目前的局限性和潜在的未来应用。本文分类如下:成体干细胞,组织更新和再生>干细胞和疾病成体干细胞,组织更新和再生>干细胞分化和逆转。
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期刊介绍: Developmental biology is concerned with the fundamental question of how a single cell, the fertilized egg, ultimately produces a complex, fully patterned adult organism. This problem is studied on many different biological levels, from the molecular to the organismal. Developed in association with the Society for Developmental Biology, WIREs Developmental Biology will provide a unique interdisciplinary forum dedicated to fostering excellence in research and education and communicating key advances in this important field. The collaborative and integrative ethos of the WIREs model will facilitate connections to related disciplines such as genetics, systems biology, bioengineering, and psychology. The topical coverage of WIREs Developmental Biology includes: Establishment of Spatial and Temporal Patterns; Gene Expression and Transcriptional Hierarchies; Signaling Pathways; Early Embryonic Development; Invertebrate Organogenesis; Vertebrate Organogenesis; Nervous System Development; Birth Defects; Adult Stem Cells, Tissue Renewal and Regeneration; Cell Types and Issues Specific to Plants; Comparative Development and Evolution; and Technologies.
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