提高细胞重编程效率和安全性的策略

Strategies to Enhance the Efficiency and Safety of Cell Reprogramming

细胞重编程是指分化的细胞在特定条件下经过去分化恢复到全能性或多能性状态,或者通过转分化将一种类型的体细胞转变成另外一种类型的细胞的过程。利用重编程技术获得的诱导型多能干细胞,谱系重编程技术获得的组织干细胞或组织细胞,具有患者特异性或者疾病特异性,可以显著减少免疫反应,同时也解决了临床细胞治疗的种子细胞来源问题,具有极大的临床应用价值。但是,另一方面,重编程效率低下和安全性问题却一直是其临床应用的瓶颈。近年来,人们围绕如何优化重编程方法进行了深入的研究,特别是对细胞重编程过程所涉及到的分子机制,包括表观遗传调控机制和上皮间质转化机制在这个过程中的作用有了更深入的认识。此外,采用非整合型载体和利用化学诱导方法替代转录因子的方式也提高了重编程的安全性。该文将就这一领域的研究进展作一综述。

Cell reprogramming refers to the process of converting somatic cells to totipotent or pluripotent stem cell by dedifferentiation, or to another type of somatic cells or somatic stem cells by transdiffertiation under certain conditions. The cells derived from patient＇s cells by reprogramming as seed cells for cell therapy, shares the specificity of patient, which could significantly reduce immune responses, provides multiple options in the source of seed cells with great value of clinical application. However, how to increase the efficiency of reprogramming and improve the safety of seed cells has been studied as a critical point in future clinic application. In recent years, researchers have been done a lot of work on how to optimize reprogramming strategy and have more comprehensive knowledge of the molecular mechanism involved in the process, such as epigenetic regulation and EMT. On the other hand, researchers adopt non-integrating episomal vectors and chemical induction to improve the safety of reprogramming. In this review, we have introduced the up-dated progress of this field.