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A brief history of organoids. ​

文献信息 ​

DOI10.1152/ajpcell.00120.2020
PMID32459504
期刊American journal of physiology. Cell physiology
影响因子4.7
JCR 分区Q1
发表年份2020
被引次数229
关键词疾病建模, 类器官, 精准医学, 再生医学
文献类型Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN0363-6143
页码C151-C165
期号319(1)
作者Claudia Corrò, Laura Novellasdemunt, Vivian S W Li

一句话小结 ​

本综述探讨了类器官技术在体外细胞培养中的重要性，强调其相较于传统单层细胞培养能够更真实地反映人体内的生物过程，尤其是在再生医学、药物发现和精准医疗等领域的应用潜力。通过回顾类器官的历史和发展，本文为未来研究提供了新的视角和思路。

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疾病建模 · 类器官 · 精准医学 · 再生医学

摘要 ​

体外细胞培养是建模人类发展和疾病的重要研究工具。尽管传统的单层细胞培养在过去被广泛使用，但由于缺乏组织结构和复杂性，这种模型未能真实反映体内的生物过程。近期的类器官技术进展彻底改变了生物医学研究的体外培养工具，通过创建强大的三维（3D）模型，重现了原代组织的细胞异质性、结构和功能。这样的类器官技术使研究人员能够在培养皿中重建人类器官和疾病，因此在再生医学、药物发现和精准医疗等许多转化应用中展现了巨大的潜力。在本综述中，我们提供了类器官的历史和发展概述，讨论了类器官的优缺点以及它们在实验室和临床中的潜在应用。

英文摘要 ​

In vitro cell cultures are crucial research tools for modeling human development and diseases. Although the conventional monolayer cell cultures have been widely used in the past, the lack of tissue architecture and complexity of such model fails to inform the true biological processes in vivo. Recent advances in the organoid technology have revolutionized the in vitro culture tools for biomedical research by creating powerful three-dimensional (3D) models to recapitulate the cellular heterogeneity, structure, and functions of the primary tissues. Such organoid technology enables researchers to recreate human organs and diseases in a dish and thus holds great promises for many translational applications such as regenerative medicine, drug discovery, and precision medicine. In this review, we provide an overview of the organoid history and development. We discuss the strengths and limitations of organoids as well as their potential applications in the laboratory and the clinic.

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主要研究问题 ​

  1. 在器官样本的创建过程中，如何确保其与真实组织的结构和功能相似？
  2. 近年来的器官技术进展有哪些关键里程碑，如何推动生物医学研究的发展？
  3. 组织工程和器官技术的结合可能会带来哪些新的应用领域？
  4. 目前器官技术在药物发现中的应用有哪些具体案例，效果如何？
  5. 在再生医学中，器官技术面临哪些伦理和技术挑战，如何克服这些挑战？

核心洞察 ​

研究背景和目的 ​

近年来，3D类器官技术的快速发展为生物医学研究提供了新的工具。传统的二维细胞培养模型在模拟体内生物过程方面存在局限性，而类器官技术能够在体外重建组织结构和功能，进而用于人类发育、疾病模型、药物筛选和再生医学等领域。本研究旨在回顾类器官的发展历程，探讨其优缺点及应用潜力。

主要方法/材料/实验设计 ​

类器官的生成主要通过以下步骤：

Mermaid diagram
  • 细胞分离：可以使用胚胎干细胞（ESCs）、诱导多能干细胞（iPSCs）或成人干细胞（ASCs）作为来源。
  • 培养基处理：通过特定的生长因子和抑制剂，诱导细胞分化。
  • 3D培养系统：使用支架或无支架技术，在三维环境中培养细胞。
  • 类器官形成：细胞自组织形成类器官。
  • 功能验证：通过实验验证类器官的功能和组织结构。

关键结果和发现 ​

  1. 技术进步：类器官技术已成功应用于多个系统，包括肠道、胃、肝脏、胰腺和大脑等，能够重建这些器官的复杂结构和功能。
  2. 疾病模型：类器官能够有效模拟多种遗传疾病和感染性疾病，例如囊性纤维化、阿尔茨海默病和Zika病毒感染。
  3. 药物筛选：患者来源的类器官（PDOs）可用于个性化药物筛选，能够预测患者对治疗的反应。

主要结论/意义/创新性 ​

类器官技术代表了生物医学研究的重大进步，提供了比传统模型更为生理相关的实验平台。它们在疾病建模、药物筛选和再生医学等领域的应用潜力巨大，能够为精准医学提供支持。

研究局限性和未来方向 ​

  1. 局限性：类器官通常缺乏周围的基质细胞和免疫细胞，可能影响其在免疫治疗中的应用。
  2. 未来方向：未来的研究应致力于改进类器官的培养方法，增强其微环境的模拟，同时探索其在再生医学和基因治疗中的应用。

比较不同模型的优缺点 ​

特性2D细胞系3D类器官PDXGEMM
建立效率低高低N/A
组织结构无有有有
细胞功能限制中等保留保留
适用性差好好不一定适用
可扩展性易有限有限N/A

通过对比，可以看出3D类器官在组织结构和细胞功能上更接近体内环境，具有更好的生物学相关性。

参考文献 ​

  1. A microfluidic 3D in vitro model for specificity of breast cancer metastasis to bone. - Simone Bersini;Jessie S Jeon;Gabriele Dubini;Chiara Arrigoni;Seok Chung;Joseph L Charest;Matteo Moretti;Roger D Kamm - Biomaterials (2014)
  2. Identification and Correction of Mechanisms Underlying Inherited Blindness in Human iPSC-Derived Optic Cups. - David A Parfitt;Amelia Lane;Conor M Ramsden;Amanda-Jayne F Carr;Peter M Munro;Katarina Jovanovic;Nele Schwarz;Naheed Kanuga;Manickam N Muthiah;Sarah Hull;Jean-Marc Gallo;Lyndon da Cruz;Anthony T Moore;Alison J Hardcastle;Peter J Coffey;Michael E Cheetham - Cell stem cell (2016)
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  4. Generation of tissue-engineered small intestine using embryonic stem cell-derived human intestinal organoids. - Stacy R Finkbeiner;Jennifer J Freeman;Minna M Wieck;Wael El-Nachef;Christopher H Altheim;Yu-Hwai Tsai;Sha Huang;Rachel Dyal;Eric S White;Tracy C Grikscheit;Daniel H Teitelbaum;Jason R Spence - Biology open (2015)
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  8. Organoid cultures derived from patients with advanced prostate cancer. - Dong Gao;Ian Vela;Andrea Sboner;Phillip J Iaquinta;Wouter R Karthaus;Anuradha Gopalan;Catherine Dowling;Jackline N Wanjala;Eva A Undvall;Vivek K Arora;John Wongvipat;Myriam Kossai;Sinan Ramazanoglu;Luendreo P Barboza;Wei Di;Zhen Cao;Qi Fan Zhang;Inna Sirota;Leili Ran;Theresa Y MacDonald;Himisha Beltran;Juan-Miguel Mosquera;Karim A Touijer;Peter T Scardino;Vincent P Laudone;Kristen R Curtis;Dana E Rathkopf;Michael J Morris;Daniel C Danila;Susan F Slovin;Stephen B Solomon;James A Eastham;Ping Chi;Brett Carver;Mark A Rubin;Howard I Scher;Hans Clevers;Charles L Sawyers;Yu Chen - Cell (2014)
  9. Zika virus impairs growth in human neurospheres and brain organoids. - Patricia P Garcez;Erick Correia Loiola;Rodrigo Madeiro da Costa;Luiza M Higa;Pablo Trindade;Rodrigo Delvecchio;Juliana Minardi Nascimento;Rodrigo Brindeiro;Amilcar Tanuri;Stevens K Rehen - Science (New York, N.Y.) (2016)
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引用本文的文献 ​

  1. An American Physiological Society cross-journal Call for Papers on "Deconstructing Organs: Single-Cell Analyses, Decellularized Organs, Organoids, and Organ-on-a-Chip Models". - Josephine C Adams;P Darwin Bell;Sue C Bodine;Heddwen L Brooks;Nigel Bunnett;Bina Joe;Kara Hansell Keehan;Thomas R Kleyman;André Marette;Rory E Morty;Jan-Marino Ramírez;Morten B Thomsen;Bill J Yates;Irving H Zucker - American journal of physiology. Lung cellular and molecular physiology (2020)
  2. A Review on the Current Knowledge on ZIKV Infection and the Interest of Organoids and Nanotechnology on Development of Effective Therapies against Zika Infection. - Samanta Gasco;María Ángeles Muñoz-Fernández - International journal of molecular sciences (2020)
  3. 3D Cell Cultures as Prospective Models to Study Extracellular Vesicles in Cancer. - Guillermo Bordanaba-Florit;Iratxe Madarieta;Beatriz Olalde;Juan M Falcón-Pérez;Félix Royo - Cancers (2021)
  4. Organoid research in digestive system tumors. - Xiaoxiao Yang;Xuewen Xu;Haitao Zhu;Ming Wang;Dongqing Wang - Oncology letters (2021)
  5. Cultures and cures: neurodiversity and brain organoids. - Andrew J Barnhart;Kris Dierickx - BMC medical ethics (2021)
  6. Patient-Derived Cancer Organoids for Precision Oncology Treatment. - Mark N Pernik;Cylaina E Bird;Jeffrey I Traylor;Diana D Shi;Timothy E Richardson;Samuel K McBrayer;Kalil G Abdullah - Journal of personalized medicine (2021)
  7. The Application of the Tissue Microarray (TMA) Technology to Analyze Cerebral Organoids. - Ida Biunno;Emanuela Paiola;Pasquale De Blasio - The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society (2021)
  8. The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update. - Joseph Azar;Hisham F Bahmad;Darine Daher;Maya M Moubarak;Ola Hadadeh;Alissar Monzer;Samar Al Bitar;Mohamed Jamal;Mohamed Al-Sayegh;Wassim Abou-Kheir - International journal of molecular sciences (2021)
  9. In Vitro Strategies to Vascularize 3D Physiologically Relevant Models. - Alessandra Dellaquila;Chau Le Bao;Didier Letourneur;Teresa Simon-Yarza - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2021)
  10. Two Sides to Every Question: Attempts to Activate Chicken Innate Immunity in 2D and 3D Hepatic Cell Cultures. - Csilla Sebők;Patrik Tráj;Júlia Vörösházi;Máté Mackei;Márton Papp;Péter Gálfi;Zsuzsanna Neogrády;Gábor Mátis - Cells (2021)

... (219 更多 篇文献)

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