Human organoids: model systems for human biology and medicine.

文献信息

DOI	10.1038/s41580-020-0259-3
PMID	32636524
期刊	Nature reviews. Molecular cell biology
影响因子	90.2
JCR 分区	Q1
发表年份	2020
被引次数	935
关键词	人类类器官, 生物医学, 疾病模型, 干细胞, 3D培养
文献类型	Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN	1471-0072
页码	571-584
期号	21(10)
作者	Jihoon Kim, Bon-Kyoung Koo, Juergen A Knoblich

一句话小结

随着人类类器官技术的发展，研究人员能够以更高的精细度重现人类器官的结构和功能，从而为研究人类特有的生物学和疾病提供了新的平台。本文综述了人类类器官在疾病模型中的应用及其优势，同时指出了减少对动物实验依赖所面临的挑战。

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人类类器官 · 生物医学 · 疾病模型 · 干细胞 · 3D培养

摘要

生物研究历史上对动物模型的依赖，有时使得解决特定于人类生物学和疾病理解的问题变得具有挑战性。然而，随着人类类器官的出现——这些是源自干细胞的三维培养系统——现在可以在惊人的细节中重现人类器官的结构和生理。人类类器官为研究人类疾病提供了独特的机会，并补充了动物模型。人类类器官已被用于通过基因工程改造人类干细胞来研究传染病、遗传疾病和癌症，同时也可以直接从患者活检样本生成类器官进行研究。这篇综述讨论了人类类器官作为发育和疾病模型的应用、优缺点，并概述了为了使类器官能够显著减少动物实验需求而需克服的挑战。

英文摘要

The historical reliance of biological research on the use of animal models has sometimes made it challenging to address questions that are specific to the understanding of human biology and disease. But with the advent of human organoids - which are stem cell-derived 3D culture systems - it is now possible to re-create the architecture and physiology of human organs in remarkable detail. Human organoids provide unique opportunities for the study of human disease and complement animal models. Human organoids have been used to study infectious diseases, genetic disorders and cancers through the genetic engineering of human stem cells, as well as directly when organoids are generated from patient biopsy samples. This Review discusses the applications, advantages and disadvantages of human organoids as models of development and disease and outlines the challenges that have to be overcome for organoids to be able to substantially reduce the need for animal experiments.

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主要研究问题

核心洞察

研究背景和目的

随着生物医学研究对人类生物学和疾病理解的深入，传统的动物模型逐渐显现出其局限性，特别是在与人类特有的生物过程和疾病机制相关的研究中。人类类器官的出现为解决这些问题提供了新的可能性。类器官是源自干细胞的三维培养系统，能够在体外重建人类器官的结构和生理功能。本研究旨在探讨人类类器官在疾病模型、药物筛选和生物医学研究中的应用、优势与挑战。

主要方法/材料/实验设计

类器官的建立主要包括以下几个步骤：

干细胞选择：
- 使用诱导性多能干细胞（iPSCs）或成人干细胞（AdSCs）作为起始材料。
分化诱导：
- 通过特定的生长因子和信号通路调节因子，诱导干细胞向目标组织类型分化。
- 采用逐步诱导的方式，模拟人类发育过程。
三维培养：
- 在三维基质中培养细胞，使其自组装形成类器官。

以下是类器官建立的流程图示例：

关键结果和发现

类器官的生理特性：人类类器官能够模拟多种人类器官的生理特性，且在基因组编辑和药物筛选中表现出良好的应用潜力。
疾病建模：类器官已被成功用于研究多种人类疾病，包括感染性疾病、遗传性疾病和癌症。
个性化医疗：通过患者来源的类器官，研究者能够进行个性化的药物筛选，评估不同患者对药物的反应。

主要结论/意义/创新性

人类类器官技术为生物医学研究提供了更为人性化的模型，能够更好地反映人类生理和病理状态。这种技术的进步不仅提升了疾病模型的准确性，也为个性化医疗和新药开发提供了重要的平台。尽管类器官技术仍处于发展阶段，但其潜力巨大，有望在未来的生物医学研究中发挥更重要的作用。

研究局限性和未来方向

技术局限性：类器官技术仍需解决标准化、细胞组成的多样性和培养条件的优化等问题。
复杂性挑战：随着研究的深入，如何在类器官中加入更多的细胞类型和组织结构以更好地模拟人体生理仍然是一个挑战。
未来方向：未来的研究应聚焦于提高类器官的功能性、降低培养成本、建立更为标准化的培养流程，并探索类器官与其他生物模型的结合，如“器官在芯片”技术，以实现更复杂的人体生理模拟。

参考文献

Progress and potential in organoid research. - Giuliana Rossi;Andrea Manfrin;Matthias P Lutolf - Nature reviews. Genetics (2018)
Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. - Toshiro Sato;Daniel E Stange;Marc Ferrante;Robert G J Vries;Johan H Van Es;Stieneke Van den Brink;Winan J Van Houdt;Apollo Pronk;Joost Van Gorp;Peter D Siersema;Hans Clevers - Gastroenterology (2011)
Human Intestinal Organoids Maintain Self-Renewal Capacity and Cellular Diversity in Niche-Inspired Culture Condition. - Masayuki Fujii;Mami Matano;Kohta Toshimitsu;Ai Takano;Yohei Mikami;Shingo Nishikori;Shinya Sugimoto;Toshiro Sato - Cell stem cell (2018)
Cerebral organoids model human brain development and microcephaly. - Madeline A Lancaster;Magdalena Renner;Carol-Anne Martin;Daniel Wenzel;Louise S Bicknell;Matthew E Hurles;Tessa Homfray;Josef M Penninger;Andrew P Jackson;Juergen A Knoblich - Nature (2013)
Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. - Minoru Takasato;Pei X Er;Han S Chiu;Barbara Maier;Gregory J Baillie;Charles Ferguson;Robert G Parton;Ernst J Wolvetang;Matthias S Roost;Susana M Chuva de Sousa Lopes;Melissa H Little - Nature (2015)
Long-Term Expansion of Functional Mouse and Human Hepatocytes as 3D Organoids. - Huili Hu;Helmuth Gehart;Benedetta Artegiani;Carmen LÖpez-Iglesias;Florijn Dekkers;Onur Basak;Johan van Es;Susana M Chuva de Sousa Lopes;Harry Begthel;Jeroen Korving;Maaike van den Born;Chenhui Zou;Corrine Quirk;Luis Chiriboga;Charles M Rice;Stephanie Ma;Anne Rios;Peter J Peters;Ype P de Jong;Hans Clevers - Cell (2018)
Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium. - Margherita Y Turco;Lucy Gardner;Jasmine Hughes;Tereza Cindrova-Davies;Maria J Gomez;Lydia Farrell;Michael Hollinshead;Steven G E Marsh;Jan J Brosens;Hilary O Critchley;Benjamin D Simons;Myriam Hemberger;Bon-Kyoung Koo;Ashley Moffett;Graham J Burton - Nature cell biology (2017)
Modeling mouse and human development using organoid cultures. - Meritxell Huch;Bon-Kyoung Koo - Development (Cambridge, England) (2015)
Organoids: A historical perspective of thinking in three dimensions. - Marina Simian;Mina J Bissell - The Journal of cell biology (2017)
Organogenesis in a dish: modeling development and disease using organoid technologies. - Madeline A Lancaster;Juergen A Knoblich - Science (New York, N.Y.) (2014)

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... (925 更多篇文献)

Human organoids: model systems for human biology and medicine. ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

研究背景和目的 ​

主要方法/材料/实验设计 ​

关键结果和发现 ​

主要结论/意义/创新性 ​

研究局限性和未来方向 ​

参考文献 ​

引用本文的文献 ​