动物细胞永生化研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2024-0020

生物技术通报 ›› 2024, Vol. 40 ›› Issue (7): 78-89.doi: 10.13560/j.cnki.biotech.bull.1985.2024-0020

动物细胞永生化研究进展

张震宇¹^,²^,³(), 靳莉武¹^,²^,³, 王婧尊¹^,²^,³, 田玲¹^,²^,³, 乔自林¹^,²^,⁴, 杨迪¹^,²^,⁵, 阿依木古丽·阿不都热依木¹^,³()

1.西北民族大学生物医学研究中心甘肃省动物细胞技术创新中心, 兰州 730030
2.西北民族大学生物医学研究中心细胞基质疫苗关键技术与产业化教育部工程研究中心, 兰州 730030
3.西北民族大学生命科学与工程学院，兰州 730030
4.西北民族大学生物医学研究中心生物工程与技术国家民委重点实验室, 兰州 730030
5.西北民族大学实验教学部, 兰州 730030

收稿日期:2024-01-05 出版日期:2024-07-26 发布日期:2024-07-30
通讯作者: 阿依木古丽·阿不都热依木，教授，研究方向：动物细胞工程（疫苗方向）、基础兽医学；E-mail: Ayimgul80@xbmu.edu.cn
作者简介:张震宇，男，硕士研究生，研究方向：动物细胞工程；E-mail: 375470311@qq.com
基金资助:
甘肃省科技计划重点研发项目(23YFFA0071);中央高校基本科研业务费项目(31920220070);中央高校基本科研业务费项目(31920230001);甘肃省科技计划项目(22JR11RA239)

Research Progress in the Immortalization of Animal Cells

ZHANG Zhen-yu¹^,²^,³(), JIN Li-wu¹^,²^,³, WANG Jing-zun¹^,²^,³, TIAN Ling¹^,²^,³, QIAO Zi-lin¹^,²^,⁴, YANG Di¹^,²^,⁵, AYIMUGULI Abudureyimu¹^,³()

1. Gansu Tech Innovation Center of Animal Cell, Biomedical Research Center, Northwest Minzu University, Lanzhou 730030
2. Engineering Research Center for Key Technologies and Industrialization of Cell-Based Vaccines, Ministry of Education, Biomedical Research Center, Northwest Minzu University, Lanzhou 730030
3. College of Life Science and Engineering, Northwest Minzu University, Lanzhou 730030
4. Key Laboratory of Bioengineering and Technology State Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou 730030
5. Department of Experiment Teaching, Northwest Minzu University, Lanzhou 730030

Received:2024-01-05 Published:2024-07-26 Online:2024-07-30

摘要/Abstract

摘要：

细胞永生化是指通过各种手段、方式来突破原代细胞衰老的限制，延长细胞寿命，实现细胞无限复制增殖，是当前生物医学领域研究的一个热点与难点。永生化细胞株/系可用于生物制品研发、衰老机制探索以延伸生命等；然而目前永生化细胞种类不多、永生化技术相对较难，肿瘤风险以及动物福利伦理等原因，还不能满足研发需求。目的细胞永生化不仅可以永久保存动物细胞遗传资源，还对多种疾病的诊断、治疗及细胞基质疫苗的研发等提供支持。本文就动物细胞永生化的原理、永生化机制及方法的研究最新进展进行综述，为未来的生物医学研究和应用提供参考。

关键词: 动物细胞, 细胞永生化, 永生化机制, 永生化方法

Abstract:

Cell immortalization refers to breaking through the limitations of primary cell aging, extending cell lifespan, and achieving unlimited cell replication and proliferation through various means and methods, which is a hot and difficult research topic in the current biomedical field. Immortalized cell lines can be used for the development of biological products, exploration of aging mechanisms to extend life, etc. However, due to the limited variety of immortalized cells, relatively difficult immortalization technology, tumor risk, and animal welfare ethics, it still cannot meet the research and developing needs. The purpose of immortalizing cells is not only to permanently preserve the genetic resources of animal cells, but also to provide support for the diagnosis and treatment of various diseases, as well as to develop cell matrix for vaccines. This article reviews the latest progresses in the principles, mechanisms, and methods of immortaling animal cells, providing reference for future biomedical research and applications.

Key words: animal cells, cell immortalizing, immortalization mechanism, immortalization method

张震宇, 靳莉武, 王婧尊, 田玲, 乔自林, 杨迪, 阿依木古丽·阿不都热依木. 动物细胞永生化研究进展[J]. 生物技术通报, 2024, 40(7): 78-89.

ZHANG Zhen-yu, JIN Li-wu, WANG Jing-zun, TIAN Ling, QIAO Zi-lin, YANG Di, AYIMUGULI Abudureyimu. Research Progress in the Immortalization of Animal Cells[J]. Biotechnology Bulletin, 2024, 40(7): 78-89.

图/表 4

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物种 Species	细胞系名称 Cell line name	细胞系来源 Cell line source	参考文献 Reference
兔 Rabbit	HIG-82	兔膝关节成纤维细胞 Rabbit knee joint fibroblasts	[29]
人 Human	ECV304	人脐静脉内皮细胞Human umbilical vein endothelial cells	[30]
兔 Rabbit	RCE1	兔角膜上皮细胞 Rabbit corneal epithelial cells	[31]
兔 Rabbit	iRCEC	兔角膜内皮细胞 Rabbit corneal endothelial cells	[32]
鸡 Chicken	DF-1	鸡胚胎成纤维细胞 Chicken embryo fibroblasts	[33]
豚鼠 Guinea pig	GPK- si	豚鼠肾细胞 Guinea pig kidney cells	[34]

物种 Species	细胞系名称 Cell line name	细胞系来源 Cell line source	参考文献 Reference
兔 Rabbit	HIG-82	兔膝关节成纤维细胞 Rabbit knee joint fibroblasts	[29]
人 Human	ECV304	人脐静脉内皮细胞Human umbilical vein endothelial cells	[30]
兔 Rabbit	RCE1	兔角膜上皮细胞 Rabbit corneal epithelial cells	[31]
兔 Rabbit	iRCEC	兔角膜内皮细胞 Rabbit corneal endothelial cells	[32]
鸡 Chicken	DF-1	鸡胚胎成纤维细胞 Chicken embryo fibroblasts	[33]
豚鼠 Guinea pig	GPK- si	豚鼠肾细胞 Guinea pig kidney cells	[34]

细胞 Cells	传代次数 Cell passages	细胞系名称 Cell line name	永生化方式 Immortalization method	生物学特性 Biological characteristics
猪精原干细胞 Porcine spermatogonial stem cells	>35代 Over 35 passages	Ttag and Puro	SV40LT	未出现形态改变及多核细胞^[54]
人角膜干细胞 Human corneal stromal stem cells	>15代 Over 15 passages	SV40T-imCSSC	SV40LT	保留干细胞特性，具有抗炎特性^[55]
小鼠肠平滑肌细胞 Mouse intestinal smooth muscle cells	至50代 Up to 50 passages	ISMC- Hc	SV40LT	与原代肠平滑肌细胞（ISMC）特征基本一致，增殖活性更强，且无致瘤性^[56]
人牙髓干细胞 Human dental pulp stem cells	>15代 Over 15 passages	TERT	hTERT	增殖速度增快，且维持干细胞特性^[57]
胎牛皮肤成纤维细胞 Fetal bovine skin fibroblasts	>50代 Over 50 passages	hTERT-CSF	hTERT	增殖速度更快，且无多核细胞^[58]
猪耳、胎儿和肺组织源成纤维细胞 Primary fibroblasts prepared from pig ear, fetal and lung tissues	30-45代 30-45 passages	Fibroblast cell line	hTERT	无细胞特性改变，增值代次增加，但SLA I类基因略有上调^[59]
猪肺源巨噬细胞 Porcine lung-derived monocyte-derived macrophages	>54代 Over 54 passages	IPLuM	SV40LT和pTERT	保持巨噬细胞形态，对ASFV易感^[60]
猪小肠巨噬细胞 Porcine intestinal macrophages	>50代 Over 50 passages	IPIM	SV40LT和pTERT	保留巨噬细胞特征，对PRRSV敏感性增加^[61]
牦牛瘤胃上皮细胞 Epithelial cells of the rumen stomach of yaks	>30代 Over 30 passages	SV40T-YREC-hTERT	SV40LT和hTERT	保留上皮细胞特性，无多核细胞^[62]

细胞 Cells	传代次数 Cell passages	细胞系名称 Cell line name	永生化方式 Immortalization method	生物学特性 Biological characteristics
猪精原干细胞 Porcine spermatogonial stem cells	>35代 Over 35 passages	Ttag and Puro	SV40LT	未出现形态改变及多核细胞^[54]
人角膜干细胞 Human corneal stromal stem cells	>15代 Over 15 passages	SV40T-imCSSC	SV40LT	保留干细胞特性，具有抗炎特性^[55]
小鼠肠平滑肌细胞 Mouse intestinal smooth muscle cells	至50代 Up to 50 passages	ISMC- Hc	SV40LT	与原代肠平滑肌细胞（ISMC）特征基本一致，增殖活性更强，且无致瘤性^[56]
人牙髓干细胞 Human dental pulp stem cells	>15代 Over 15 passages	TERT	hTERT	增殖速度增快，且维持干细胞特性^[57]
胎牛皮肤成纤维细胞 Fetal bovine skin fibroblasts	>50代 Over 50 passages	hTERT-CSF	hTERT	增殖速度更快，且无多核细胞^[58]
猪耳、胎儿和肺组织源成纤维细胞 Primary fibroblasts prepared from pig ear, fetal and lung tissues	30-45代 30-45 passages	Fibroblast cell line	hTERT	无细胞特性改变，增值代次增加，但SLA I类基因略有上调^[59]
猪肺源巨噬细胞 Porcine lung-derived monocyte-derived macrophages	>54代 Over 54 passages	IPLuM	SV40LT和pTERT	保持巨噬细胞形态，对ASFV易感^[60]
猪小肠巨噬细胞 Porcine intestinal macrophages	>50代 Over 50 passages	IPIM	SV40LT和pTERT	保留巨噬细胞特征，对PRRSV敏感性增加^[61]
牦牛瘤胃上皮细胞 Epithelial cells of the rumen stomach of yaks	>30代 Over 30 passages	SV40T-YREC-hTERT	SV40LT和hTERT	保留上皮细胞特性，无多核细胞^[62]

动物细胞永生化研究进展

Research Progress in the Immortalization of Animal Cells

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