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Organoids.

文献信息

DOI10.1038/s43586-022-00174-y
PMID37325195
期刊Nature reviews. Methods primers
影响因子56.0
JCR 分区Q1
发表年份2022
被引次数348
关键词类器官, 组织工程, 疾病模型, 药物发现, 个性化医疗
文献类型Journal Article
ISSN2662-8449
期号2()
作者Zixuan Zhao, Xinyi Chen, Anna M Dowbaj, Aleksandra Sljukic, Kaitlin Bratlie, Luda Lin, Eliza Li Shan Fong, Gowri Manohari Balachander, Zhaowei Chen, Alice Soragni, Meritxell Huch, Yi Arial Zeng, Qun Wang, Hanry Yu

一句话小结

类器官作为一种有效的体外模型,能够重现体内组织的复杂结构和功能,广泛应用于人类组织发展、再生、疾病建模和药物发现等领域。本文强调了在工程类器官过程中选择和开发材料及方法的重要性,并讨论了生成稳健类器官的关键考虑因素及未来的研究优先事项。

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类器官 · 组织工程 · 疾病模型 · 药物发现 · 个性化医疗

摘要

类器官因其简便的组织工程细胞基础体外模型而受到越来越多的关注,这些模型重现了相应体内组织复杂结构和功能的许多方面。类器官可以被解剖和探究,以进行关于人类组织发展、再生和修复的基本机制研究。类器官还可用于诊断、疾病建模、药物发现和个性化医学。类器官的来源可以是多能干细胞或组织驻留干细胞(胚胎或成人),也可以是来自健康或病变组织(如肿瘤)的前体细胞或分化细胞。迄今为止,已有多种类器官工程策略被报道,以支持类器官的培养、增长、增殖、分化和成熟。本指南旨在强调选择和开发这些材料和方法以控制细胞/组织微环境的理论基础;因此,也影响了工程类器官的结构和功能。我们还讨论了生成稳健类器官的关键考虑因素,例如与细胞分离和接种、基质和可溶因子选择、物理信号和整合相关的因素。还概述了类器官领域内数据质量、可重复性和存储的一般标准。最后,我们通过详细阐述类器官在不同应用中的局限性,以及未来几年类器官工程的关键优先事项,来结束本文。

英文摘要

Organoids have attracted increasing attention because they are simple tissue-engineered cell-based in vitro models that recapitulate many aspects of the complex structure and function of the corresponding in vivo tissue. They can be dissected and interrogated for fundamental mechanistic studies on development, regeneration, and repair in human tissues. Organoids can also be used in diagnostics, disease modeling, drug discovery, and personalized medicine. Organoids are derived from either pluripotent or tissue-resident stem (embryonic or adult) or progenitor or differentiated cells from healthy or diseased tissues, such as tumors. To date, numerous organoid engineering strategies that support organoid culture and growth, proliferation, differentiation and maturation have been reported. This Primer serves to highlight the rationale underlying the selection and development of these materials and methods to control the cellular/tissue niche; and therefore, structure and function of the engineered organoid. We also discuss key considerations for generating robust organoids, such as those related to cell isolation and seeding, matrix and soluble factor selection, physical cues and integration. The general standards for data quality, reproducibility and deposition within the organoid community is also outlined. Lastly, we conclude by elaborating on the limitations of organoids in different applications, and key priorities in organoid engineering for the coming years.

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主要研究问题

  1. 在器官样本的工程化过程中,如何选择合适的基质和可溶性因子以优化类器官的生长和分化?
  2. 类器官在个性化医疗中的具体应用案例有哪些?它们如何影响疾病治疗策略?
  3. 针对不同类型的组织,类器官的培养和成熟过程中存在哪些特定的挑战?
  4. 在药物发现中,类器官如何帮助研究人员理解药物的作用机制及其潜在副作用?
  5. 未来几年内,类器官工程领域的研究重点和技术进展预期会有哪些方向?

核心洞察

研究背景和目的

类器官因其能够模拟体内组织的复杂结构和功能而受到广泛关注。它们作为简单的组织工程细胞模型,能够用于研究人类组织的发展、再生和修复的基本机制。类器官在诊断、疾病建模、药物发现和个性化医疗等领域具有重要应用。本研究旨在强调类器官工程的材料和方法选择的合理性,以控制细胞/组织生态位,从而影响类器官的结构和功能。

主要方法/材料/实验设计

本研究探讨了类器官生成的关键考虑因素,包括细胞分离和播种、基质和可溶因子的选择、物理信号及其整合。以下是技术路线的流程图:

Mermaid diagram

关键结果和发现

  • 类器官的生成依赖于细胞的类型选择,包括多能干细胞、组织常驻干细胞或从健康或病变组织(如肿瘤)中分化的细胞。
  • 报告了多种类器官工程策略,这些策略支持类器官的培养、生长、增殖、分化和成熟。
  • 强调了数据质量、可重复性和在类器官社区内的数据存储标准的重要性。

主要结论/意义/创新性

类器官技术的进步为基础生物医学研究和临床应用提供了新的平台。通过合理选择材料和方法,可以优化类器官的结构和功能,推动疾病模型和个性化医疗的发展。研究还强调了在类器官工程中的关键优先事项,为未来的研究指明了方向。

研究局限性和未来方向

  • 类器官在某些应用中的局限性,如缺乏完整的微环境和血管化。
  • 未来的研究应集中在改进类器官的功能性和复杂性,以更好地模拟体内环境,推动其在药物筛选和疾病治疗中的应用。
部分内容
研究背景和目的类器官用于模拟组织功能,应用于疾病研究和个性化医疗
主要方法/材料/实验设计细胞分离、播种、基质和可溶因子选择、物理信号整合,最终生成类器官
关键结果和发现报告了多种类器官工程策略,强调数据质量和可重复性的重要性
主要结论/意义/创新性优化类器官的结构和功能,推动基础研究和临床应用的发展
研究局限性和未来方向类器官在模拟微环境和血管化方面的局限,未来研究需改进类器官的功能性和复杂性

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引用本文的文献

  1. Patient-Derived Organoids: The Beginning of a New Era in Ovarian Cancer Disease Modeling and Drug Sensitivity Testing. - Iason Psilopatis;Alexandros G Sykaras;Georgios Mandrakis;Kleio Vrettou;Stamatios Theocharis - Biomedicines (2022)
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  3. A Beginner's Guide to Cell Culture: Practical Advice for Preventing Needless Problems. - Sabine Weiskirchen;Sarah K Schröder;Eva Miriam Buhl;Ralf Weiskirchen - Cells (2023)
  4. Primary human organoids models: Current progress and key milestones. - Giuseppe Calà;Beatrice Sina;Paolo De Coppi;Giovanni Giuseppe Giobbe;Mattia Francesco Maria Gerli - Frontiers in bioengineering and biotechnology (2023)
  5. Revolutionizing Disease Modeling: The Emergence of Organoids in Cellular Systems. - Rita Silva-Pedrosa;António José Salgado;Pedro Eduardo Ferreira - Cells (2023)
  6. Advanced In Vitro Three-Dimensional Skin Models of Atopic Dermatitis. - Hye-Jeong Jang;Jung Bok Lee;Jeong-Kee Yoon - Tissue engineering and regenerative medicine (2023)
  7. Patient Derived Organoids (PDOs), Extracellular Matrix (ECM), Tumor Microenvironment (TME) and Drug Screening: State of the Art and Clinical Implications of Ovarian Cancer Organoids in the Era of Precision Medicine. - Giulia Spagnol;Francesca Sensi;Orazio De Tommasi;Matteo Marchetti;Giulio Bonaldo;Livia Xhindoli;Marco Noventa;Marco Agostini;Roberto Tozzi;Carlo Saccardi - Cancers (2023)
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... (338 更多 篇文献)


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