重编程细胞的命运

摘要

背景：体细胞重新编程技术也称细胞重组技术，使已经完成分化的体细胞回到原始的全能性或多能性状态，并可以重新分化成与原来不一样的细胞。通过重编程技术可以获得患者特异性诱导多能干细胞和疾病特异性诱导多能干细胞，显著减少了免疫排斥反应。目的：探讨关于直接重编程到特定系的方法，总结参与重编程的分子机制。方法：以“重编程”为中文检索词，“reprogramming”为英文检索词，应用计算机检索维普(VIP)期刊全文数据库、万方全文数据库、中国知网全文数据库、PubMed 数据库、Springer 数据库1958年1月至2015年4月有关细胞重编程技术的文献，排除与研究目的无关及重复性研究，保留40篇文献进一步分析。结果与结论：当前重编程的步骤效率很低，在特定群只有相对少量的细胞能进行重编程，重编程的完整性和程度也有待证实。直接重编程成体、定系的细胞从一种细胞到另一种细胞一直是发育生物学很难达到的目标。最近的研究证明分化的细胞强制表达特异转录因子能促进细胞分化。这些发现使再生医学领域有了重大进展，可以提供替代细胞治疗各种再生紊乱。目前，基本的分子机制需要进一步阐明，在直接重编程被应用于临床之前还有许多问题需要解决。%BACKGROUND:Somatic cel reprogramming technology, also known as recombinant technology, has completed differentiated somatic cels back to the original totipotent or pluripotent state, and can be re-differentiated into cels different from original ones. Re-programming techniques are able to harvest specificaly induced pluripotent stem cels and disease-specific induced pluripotent stem cels from patients, which can significantly reduce the immune rejection. OBJECTIVE: To explore the method from direct reprogramming to specific cel lines and to conclude the molecular mechanisms underlying reprogramming. METHODS:A computer-based search of VIP, Wanfang, CNKI, PubMed and Springer databases was performed for articles related to cel reprogramming techniques published from January 1958 to April 2015 using the keywords of “reprogramming” in Chinese and English, respectively. After elimination of unrelated and repetitive studies, 40 articles were retained for further analysis. RESULTS AND CONCLUSION:Current reprogramming steps are inefficient that in the specific group only a relatively smal number of cels can be reprogrammed, and the extent and integrity of reprogramming are questionable. Direct reprogramming of adult cels and specific cel lines that are changed to another line is always a difficulty in developmental biology. Recent studies have proved that differentiated cels can forcibly express specific transcription factor to improve cel differentiation. This discovery is a great progress in regenerative medicine that cel replacement therapy can be provided for renewable disorders. At present, the basic molecular mechanisms require further clarification, and there are many problems to be solved before the direct reprogramming is used clinicaly.