类器官培养基主要成分的作用机制及潜在功能

doi:10.12307/2021.153

中国组织工程研究 ›› 2021, Vol. 25 ›› Issue (31): 5072-5078.doi: 10.12307/2021.153

• 干细胞综述 stem cell review • 上一篇下一篇

类器官培养基主要成分的作用机制及潜在功能

刘琦1，2，姚茜1，3 ，韦正波2，谢莹1，3

1广西医科大学生命科学研究院，广西壮族自治区南宁市 530021；2广西医科大学附属肿瘤医院，广西壮族自治区南宁市 530021；3广西区域性高发肿瘤早期防治研究教育部重点实验室，广西壮族自治区南宁市 530021

收稿日期:2020-11-17 修回日期:2020-11-19 接受日期:2021-01-08 出版日期:2021-11-08 发布日期:2021-04-25
通讯作者: 韦正波，博士，主任医师，广西医科大学附属肿瘤医院，广西壮族自治区南宁市 530021
作者简介:刘琦，女，1994年生，黑龙江省齐齐哈尔市人，汉族，广西医科大学在读硕士，主要从事类器官相关研究。
基金资助:
国家自然科学基金地区基金项目(81760361)，项目负责人：韦正波；广西自然科学基金面上项目(2017GXNSFAA198064)，项目负责人：谢莹；区域性高发肿瘤早期防治研究教育部重点实验室自主研究项目(GKE2018-07)，项目负责人：谢莹

Action mechanism and potential function on main components of organoid culture medium

Liu Qi1, 2, Yao Xi1, 3 , Wei Zhengbo2, Xie Ying1, 3

1Life Science Institute, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China; 2Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China; 3Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning 530021, Guangxi Zhuang Autonomous Region, China

Received:2020-11-17 Revised:2020-11-19 Accepted:2021-01-08 Online:2021-11-08 Published:2021-04-25
Contact: Wei Zhengbo, MD, Chief physician, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
About author:Liu Qi, Master candidate, Life Science Institute, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China; Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Supported by:
the National Natural Science Foundation of China, No. 81760361 (to WZB); General Project of Guangxi Natural Science Foundation of China, No. 2017GXNSFAA198064 (to XY); Autonomous Research Project of Key Laboratory of Ministry of Education for Early Prevention and Treatment of Regional High Frequency Tumor, No. GKE2018-07 (to XY)

摘要/Abstract

摘要：

文题释义：

类器官：指通过体外三维立体培养，产生和体内器官具有相似结构和功能的培养物，由包括干细胞在内的多种细胞组成，具有向多种器官分化的潜能，能更好地代表体内的生理和遗传特征。
细胞因子：体内的免疫细胞和一些具有分泌功能的非免疫细胞经刺激后会合成和分泌一些小分子蛋白，而这些对细胞增殖、分化、凋亡等生物学功能具有调控作用的小分子蛋白就是细胞因子。
背景：传统的2D细胞培养由于简便易操作成为细胞培养的主导方式，但其因无法模拟细胞在体内的生长方式、微环境、维持遗传稳定性等特性而备受质疑。类器官培养能高度模拟人体内环境并能重现来源器官的某些功能，是目前最为可靠的细胞模型，但由于其培养条件的复杂性和差异性使得类器官培养条件尚不成熟，因此总结已有培养基主要成分并在此基础上完善类器官培养技术至关重要。
目的：综述多种组织类器官培养基的主要成分及其潜在功能，为类器官培养提供一定的理论依据。
方法：第一作者通过检索PubMed数据库、Cochrane Library数据库、CNKI数据库以及万方数据库的相关文献，检索英文关键词“organoids，cell culture，cytokines，amino acid，R-spondin-1”等，中文关键词“类器官，细胞培养，细胞因子，氨基酸”等。排除重复性以及与目的无关的文章，选取2009至2020年期间共84篇文章进行综述。
结果与结论：对于类器官培养，除基础培养基外仍需要细胞因子、氨基酸、小分子抑制剂等多种物质共同参与，不同类器官所需培养条件不尽相同，与组织来源高度相关，各成分在特定的组织来源类器官培养中发挥至关重要的作用。文章对目前已有类器官培养基主要成分进行总结，在此基础上分析各主要培养成分的作用机制，为各种类器官模型稳定构建提供一定的参考。
https://orcid.org/0000-0002-8856-4243(谢莹)

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 类器官, 培养基, 成分, 细胞因子, 氨基酸, 小分子抑制剂, 综述

Abstract: BACKGROUND: Traditional 2D cell culture has become the dominant method of cell culture due to its simplicity and easy operation. However, it is doubtful because of its inability to mimic the growth mode, microenvironment, and genetic stability of cells in the host. Organoid culture highly simulates the environment in the human body and recreates certain functions of the original organs. It is currently the most reliable cell model. However, due to the complexity and variety of the culture conditions, the organoid culture conditions are not yet mature. Therefore, it is very important to summarize the existing main culture components and improve the organoid culture technology on this basis.
OBJECTIVE: To study the main components and potential functions of various organoid culture media, providing theoretical basis for the culture of organoid establishment.
METHODS: The first author searched the related literature published from 2009 to 2020 in PubMed database, Cochrane Library database, CNKI database, and Wanfang database using the English or Chinese keywords “organoids, cell culture, cytokines, amino acid, R-spondin-1”. After excluding those repetitive and irrelevant articles to the purpose of this review, a total of 84 eligible articles were finally selected for review.
RESULTS AND CONCLUSION: In addition to the basic medium, organoid culture requires the participation of cytokines, amino acids, small molecule inhibitors and other substances. Different organoid culture requires different culture conditions, which is highly related to the source of the tissue. Each component plays a vital role in development of organoids from specific tissues. This article analyzes the detail role of each main culture component by summarizing the main existing organoid culture compound, which will provide a certain reference for the stable construction of various organoid models.

Key words: organoids, medium components, cytokines, amino acids, small molecule inhibitors, review

中图分类号:

刘琦, 姚茜, 韦正波, 谢莹. 类器官培养基主要成分的作用机制及潜在功能[J]. 中国组织工程研究, 2021, 25(31): 5072-5078.

Liu Qi, Yao Xi, Wei Zhengbo, Xie Ying. Action mechanism and potential function on main components of organoid culture medium[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(31): 5072-5078.

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引言

体外细胞培养是生命科学研究中最常用且重要的研究方法，细胞培养技术直接影响着研究结果的准确性。长期以来，2D细胞培养在培养技术中占据着重要的地位，但越来越多的证据表明2D细胞培养存在着多种弊端，如在肿瘤细胞培养过程中，随着肿瘤细胞的传代增殖，原代肿瘤细胞会逐渐丢失其原始基因特性，肿瘤异质性随之消失，无法代表原始肿瘤组织的特性[1]。此外，2D细胞培养的细胞类型单一，缺少细胞间的相互作用，无法模拟人体内环境的复杂性[2]。另外，2D细胞培养过程中细胞立体结构发生改变，细胞在培养瓶中贴壁生长，完全破坏了细胞在体内的生长环境和空间结构[1]。
随着3D细胞培养技术的兴起，以3D细胞培养技术为基础的类器官培养技术开始成为研究热点。类器官培养是一种3D细胞培养系统，旨在构建更接近于来源组织器官特性的细胞模型。DROST团队[3]曾将2D细胞和类器官模型进行了对比，发现类器官不仅能高度模拟体内细胞生长环境，保持细胞生长的空间结构，而且能更好地代表来源组织器官的生理功能和生物学特性。
目前，类器官已成功应用于病原微生物致病模型构建[4]、肿瘤研究[1]、临床药物筛选[5]、药物研发等多个领域[6]，此外，新兴的单细胞测序技术[7]、CRISPR-Cas9基因编辑技术更是为类器官研究提供了进一步发展的空间[5]。但类器官培养并不如普通2D细胞培养简便，其构建成功率与组织来源种类、来源组织质量、细胞生长阶段等多种因素有关，且培养基成分复杂。随着近年来各领域对类器官培养的重视，多种组织器官来源的类器官模型均有报道，但仍有某些类器官建模成功率低、培养条件不够稳定等问题存在，特别是在低分化肿瘤组织来源的类器官培养中，其成功率明显低于高分化肿瘤来源组织或正常组织，因此对已有类器官培养基主要成分进行总结并在此基础上完善类器官培养技术十分必要。
中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

类器官培养基主要成分的作用机制及潜在功能

Action mechanism and potential function on main components of organoid culture medium

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