de Bardet Javier Curi, Cardentey Celeste Ramírez, González Belkis López, Patrone Deanira, Mulet Idania Lores, Siniscalco Dario, Robinson-Agramonte María de Los Angeles
Department of Neurobiology, International Center for Neurological Restoration, Havana 11300, Cuba.
Department of Virology, Tropical Medicine Institute Pedro Kouri, Havana 11400, Cuba.
BioTech (Basel). 2023 Jan 28;12(1):14. doi: 10.3390/biotech12010014.
Somatic human cells can divide a finite number of times, a phenomenon known as the Hayflick limit. It is based on the progressive erosion of the telomeric ends each time the cell completes a replicative cycle. Given this problem, researchers need cell lines that do not enter the senescence phase after a certain number of divisions. In this way, more lasting studies can be carried out over time and avoid the tedious work involved in performing cell passes to fresh media. However, some cells have a high replicative potential, such as embryonic stem cells and cancer cells. To accomplish this, these cells express the enzyme telomerase or activate the mechanisms of alternative telomere elongation, which favors the maintenance of the length of their stable telomeres. Researchers have been able to develop cell immortalization technology by studying the cellular and molecular bases of both mechanisms and the genes involved in the control of the cell cycle. Through it, cells with infinite replicative capacity are obtained. To obtain them, viral oncogenes/oncoproteins, myc genes, ectopic expression of telomerase, and the manipulation of genes that regulate the cell cycle, such as p53 and Rb, have been used.
人体体细胞只能分裂有限次数,这一现象被称为海弗利克极限。它基于细胞每次完成复制周期时端粒末端的逐渐侵蚀。鉴于此问题,研究人员需要在经过一定次数的分裂后不会进入衰老阶段的细胞系。这样一来,随着时间的推移可以进行更持久的研究,并避免进行细胞传代至新鲜培养基所涉及的繁琐工作。然而,一些细胞具有较高的复制潜力,如胚胎干细胞和癌细胞。为实现这一点,这些细胞表达端粒酶或激活替代性端粒延长机制,这有利于维持其稳定端粒的长度。研究人员通过研究这两种机制以及参与细胞周期调控的基因的细胞和分子基础,已经能够开发细胞永生化技术。通过该技术,可以获得具有无限复制能力的细胞。为了获得它们,人们使用了病毒癌基因/癌蛋白、myc基因、端粒酶的异位表达以及对调控细胞周期的基因(如p53和Rb)的操纵。