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条件重编程:新一代细胞培养

Conditional reprogramming: next generation cell culture.

作者信息

Wu Xiaoxiao, Wang Shengpeng, Li Mingxing, Li Jing, Shen Jing, Zhao Yueshui, Pang Jun, Wen Qinglian, Chen Meijuan, Wei Bin, Kaboli Parham Jabbarzadeh, Du Fukuan, Zhao Qijie, Cho Chi Hin, Wang Yitao, Xiao Zhangang, Wu Xu

机构信息

Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.

South Sichuan Institute of Translational Medicine, Luzhou 646000, China.

出版信息

Acta Pharm Sin B. 2020 Aug;10(8):1360-1381. doi: 10.1016/j.apsb.2020.01.011. Epub 2020 Jan 26.

Abstract

Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to change of important biological and genetic characteristics. Recently, conditional reprogramming (CR) emerges as a novel next generation tool for long-term culture of primary epithelium cells derived from almost all origins without alteration of genetic background of primary cells. CR co-cultures primary cells with inactivated mouse 3T3-J2 fibroblasts in the presence of RHO-related protein kinase (ROCK) inhibitor Y-27632, enabling primary cells to acquire stem-like characteristics while retain their ability to fully differentiate. With only a few years' development, CR shows broad prospects in applications in varied areas including disease modeling, regenerative medicine, drug evaluation, drug discovery as well as precision medicine. This review is thus to comprehensively summarize and assess current progress in understanding mechanism of CR and its wide applications, highlighting the value of CR in both basic and translational researches and discussing the challenges faced with CR.

摘要

由于不可避免的衰老,哺乳动物细胞的长期原代培养一直很困难。传统的产生永生化细胞系的方法通常需要对基因组进行操作,这会导致重要生物学和遗传特性的改变。最近,条件重编程(CR)作为一种新型的下一代工具出现,用于几乎所有来源的原代上皮细胞的长期培养,而不会改变原代细胞的遗传背景。CR在RHO相关蛋白激酶(ROCK)抑制剂Y-27632存在的情况下,将原代细胞与灭活的小鼠3T3-J2成纤维细胞共培养,使原代细胞获得干细胞样特性,同时保留其完全分化的能力。经过短短几年的发展,CR在疾病建模、再生医学、药物评估、药物发现以及精准医学等不同领域的应用中展现出广阔前景。因此,本综述旨在全面总结和评估目前在理解CR机制及其广泛应用方面的进展,强调CR在基础研究和转化研究中的价值,并讨论CR面临的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c10f/7488362/1cc9d89bc291/fx1.jpg

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