人源类器官的研究进展及在口腔医学的展望

doi:10.3877/cma.j.issn.1674-1366.2019.02.001

中华口腔医学研究杂志(电子版) ›› 2019, Vol. 13 ›› Issue (02) : 65 -70. doi: 10.3877/cma.j.issn.1674-1366.2019.02.001

所属专题：口腔医学；文献；

中青年专家笔谈

人源类器官的研究进展及在口腔医学的展望

谭汝铿¹, 曾润玲¹, 王卓然¹, 徐萌¹^,^†(

)

^1. 中山大学光华口腔医学院·附属口腔医院，广东省口腔医学重点实验室，广州　510055

收稿日期:2019-01-04 出版日期:2019-04-01
通信作者: 徐萌

The research progress of human organoids and the prospects of application in stomatology

Rukeng Tan¹, Runling Zeng¹, Zhuoran Wang¹, Meng Xu¹^,^†()

^1. Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, China

Received:2019-01-04 Published:2019-04-01
Corresponding author: Meng Xu
About author:
Corresponding author: Xu Meng, Email: xumeng23@mail.sysu.edu.cn
Supported by:
Project supported by The National Natural Science Funds(81602384); 2018 Teaching reform and teaching quality plan-undergraduate practice teaching base construction project—Stomatological undergraduate practice teaching base of Sun Yat-sen University(52000-31911004); 2017 Teaching reform and teaching quality plan of Sun Yat-sen University (The application of self-made cutting machine to make ground tooth section in oral pathology lab); National Undergraduate Students Innovation Training Program(201810558159)

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引用本文：

谭汝铿, 曾润玲, 王卓然, 徐萌. 人源类器官的研究进展及在口腔医学的展望[J]. 中华口腔医学研究杂志(电子版), 2019, 13(02): 65-70.

Rukeng Tan, Runling Zeng, Zhuoran Wang, Meng Xu. The research progress of human organoids and the prospects of application in stomatology[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2019, 13(02): 65-70.

类器官是指在体外三维培养构建的，依赖于人造细胞外基质的多细胞团，具有自我更新、自我组织能力，并维持了其来源组织的生理结构和功能。类器官作为一种新兴的研究模型，兼具细胞系和动物模型两者的优点。其构建材料简单、培养效率高、耗时短，在疾病研究模型构建、临床药敏试验和再生医学中有良好的应用前景。类器官模型主要分为三种细胞来源类型：胚胎干细胞/诱导多能干细胞、成体干细胞、肿瘤细胞。本文将重点介绍三种细胞来源类器官最新的研究进展，并展望其在口腔医学中的应用。

关键词: 类器官, 胚胎干细胞, 诱导多能干细胞, 成体干细胞, 肿瘤

The organoid is a multicellular mass with the ability of self-renewal and self-organization in artificial extracellular matrix, which is constructed by three-dimensional culture in vitro, and it maintains the physiological structure and function of its source tissues. As a new research model, the organoid has the advantages of both cell lines and animal models. The easily material construction, high culturing efficiency and short time-consuming make it good application prospects in disease research model construction, clinical drug sensitivity test and regenerative medicine application. The organoid models can be divided into three types of cell sources: embryonic stem cells/induced pluripotent stem cells, adult stem cells and cancer cells. In this review, organoid from three cell sources will be elaborated separately, and mainly focused on the current status of human organoid research progress and the prospect of application in stomatology.

Key words: Organoid, Embryonic stem cells, Induced pluripotent stem cells, Adult stem cells, Neoplasms

图1 胚胎干细胞、诱导性多能干细胞来源的类器官培养过程

图2 已成功构建的成体干细胞来源的类器官

表1 胚胎干细胞、诱导多能干细胞来源的类器官构建材料

组织类型	组织来源	胚层分化培养基	器官分化培养基	类器官生长培养基
肠^[5]	人源胚胎干细胞和诱导性多能干细胞	含有Activin A的RPMI 1640培养基	含有成纤维细胞生长因子4、 CHIR99021的RPMI 1640培养基	含有表皮细胞生长因子、头蛋白、R-spondin1的高级DMEM/F12培养基、Matrigel
胃^[6]	人源胚胎干细胞和诱导性多能干细胞系	含有Activin A、BMP4的RPMI 1640培养基	WNT3A、CHIR99021、成纤维细胞生长因子4、头蛋白、维甲酸的RPMI 1640培养基	含有表皮细胞生长因子、头蛋白、维甲酸的高级DMEM/F12培养基、 Matrigel
肝脏^[7]	人源胚胎干细胞和诱导性多能干细胞系	含有Activin A、BMP4、CHIR 99021、成纤维细胞生长因子2、 LY294002的DMEM/F12培养基	含有成纤维细胞生长因子10、 BMP4的RPMI及B27培养基	含有肝细胞生长因子、抑瘤素M的高级DMEM/F12培养基、Matrigel
脑^[8]	人源胚胎干细胞和诱导性多能干细胞系	含有endo-IWR1、LDN-193189、 SB431542、β-巯基乙醇的KSR培养基	含有NEAA、BDNF、GDNF的neurobasal-type differentiation培养基、Matrigel	DMEM/F12培养基、Matrigel
肾^[9]	人源胚胎干细胞和诱导性多能干细胞系	含有Activin的高级RPMI培养基	含有成纤维细胞生长因子9、 CHIR99021的高级RPMI培养基	含有CHIR99021、头蛋白、成纤维细胞生长因子9的高级RPMI 1640培养基
肺^[10]	人源胚胎干细胞系	含有Activin A、BMP4的DMEM/ F12培养基	含有成纤维细胞生长因子7，CHIR - 99021、维甲酸的DMEM/ F12培养基	DMEM/F12培养基、Matrigel
乳腺^[11]	人源诱导性多能干细胞系	complete MammoCult培养基	含有成纤维细胞生长因子10、肝细胞生长因子、催乳素的EpiCult B培养基、Matrigel/CollagenⅠ	含有成纤维细胞生长因子10、肝细胞生长因子的EpiCult B培养基、 Matrigel/CollagenⅠ

表1 胚胎干细胞、诱导多能干细胞来源的类器官构建材料

组织类型	组织来源	胚层分化培养基	器官分化培养基	类器官生长培养基
肠^[5]	人源胚胎干细胞和诱导性多能干细胞	含有Activin A的RPMI 1640培养基	含有成纤维细胞生长因子4、 CHIR99021的RPMI 1640培养基	含有表皮细胞生长因子、头蛋白、R-spondin1的高级DMEM/F12培养基、Matrigel
胃^[6]	人源胚胎干细胞和诱导性多能干细胞系	含有Activin A、BMP4的RPMI 1640培养基	WNT3A、CHIR99021、成纤维细胞生长因子4、头蛋白、维甲酸的RPMI 1640培养基	含有表皮细胞生长因子、头蛋白、维甲酸的高级DMEM/F12培养基、 Matrigel
肝脏^[7]	人源胚胎干细胞和诱导性多能干细胞系	含有Activin A、BMP4、CHIR 99021、成纤维细胞生长因子2、 LY294002的DMEM/F12培养基	含有成纤维细胞生长因子10、 BMP4的RPMI及B27培养基	含有肝细胞生长因子、抑瘤素M的高级DMEM/F12培养基、Matrigel
脑^[8]	人源胚胎干细胞和诱导性多能干细胞系	含有endo-IWR1、LDN-193189、 SB431542、β-巯基乙醇的KSR培养基	含有NEAA、BDNF、GDNF的neurobasal-type differentiation培养基、Matrigel	DMEM/F12培养基、Matrigel
肾^[9]	人源胚胎干细胞和诱导性多能干细胞系	含有Activin的高级RPMI培养基	含有成纤维细胞生长因子9、 CHIR99021的高级RPMI培养基	含有CHIR99021、头蛋白、成纤维细胞生长因子9的高级RPMI 1640培养基
肺^[10]	人源胚胎干细胞系	含有Activin A、BMP4的DMEM/ F12培养基	含有成纤维细胞生长因子7，CHIR - 99021、维甲酸的DMEM/ F12培养基	DMEM/F12培养基、Matrigel
乳腺^[11]	人源诱导性多能干细胞系	complete MammoCult培养基	含有成纤维细胞生长因子10、肝细胞生长因子、催乳素的EpiCult B培养基、Matrigel/CollagenⅠ	含有成纤维细胞生长因子10、肝细胞生长因子的EpiCult B培养基、 Matrigel/CollagenⅠ

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