CAJ | 학술논문

背景：诱导性多能干细胞自发现以来一直是再生医学的研究热点，但人们过多地关注了它的运用性却忽略了安全性。目的：通过综述目前诱导性多能干细胞在动物移植研究中的表现，分析诱导性多能干细胞的安全性问题及可能原因，为今后的诱导性多能干细胞研究及临床运用提供参考。方法：以英文检索词为“induced pluripotent stem cels，safety，immune，immunogenicity，tumorigenicity， cancer，epigenomic，transplantation，Generation，Reprogramming，genomic，mutation”由第一作者检索2006至2014年PubMed数据库，查阅近年来与诱导性多能干细胞安全性相关的文献，进一步从Cel Press数据库和Nature数据库中获得文献全文阅读，最终保留发表时间较近的28篇文献。结果与结论：诱导性多能干细胞的安全性问题正引起越来越多人的重视，免疫原性、潜在的致瘤性与表观遗传学变异问题是其临床应用的主要隐患。诱导性多能干细胞的安全性问题主要来自于重编程过程，“插入式基因操作”比非插入式操作具有更大的致瘤风险。体细胞重编程后不同程度的发生了表观遗传学变异，这些变异多与被重编程细胞的“遗传记忆”有关。
배경：유도성다능간세포자발현이래일직시재생의학적연구열점，단인문과다지관주료타적운용성각홀략료안전성。목적：통과종술목전유도성다능간세포재동물이식연구중적표현，분석유도성다능간세포적안전성문제급가능원인，위금후적유도성다능간세포연구급림상운용제공삼고。방법：이영문검색사위“induced pluripotent stem cels，safety，immune，immunogenicity，tumorigenicity， cancer，epigenomic，transplantation，Generation，Reprogramming，genomic，mutation”유제일작자검색2006지2014년PubMed수거고，사열근년래여유도성다능간세포안전성상관적문헌，진일보종Cel Press수거고화Nature수거고중획득문헌전문열독，최종보류발표시간교근적28편문헌。결과여결론：유도성다능간세포적안전성문제정인기월래월다인적중시，면역원성、잠재적치류성여표관유전학변이문제시기림상응용적주요은환。유도성다능간세포적안전성문제주요래자우중편정과정，“삽입식기인조작”비비삽입식조작구유경대적치류풍험。체세포중편정후불동정도적발생료표관유전학변이，저사변이다여피중편정세포적“유전기억”유관。
BACKGROUND:Induced pluripotent stem cels have been a hotspot in regenerative medicine research since it was discovered. The clinical application of induced pluripotent stem cels is excessively focused on, but the safety issue is almost ignored. OBJECTIVE:By summarizing the application of induced pluripotent stem cels in animal experiments to analyze the safety problems of induced pluripotent stem cels and their possible reasons in order to lay a foundation for further study and clinical application of induced pluripotent stem cels. METHODS: PubMed database was retrieved by the first author for articles related to the safety of induced pluripotent stem cels published from 2006 to 2014 using the keywords of “induced pluripotent stem cels, safety, immune, immunogenicity, tumorigenicity, cancer, epigenomic, transplantation, generation, reprogramming,genomic, mutation” in English. Related ful texts were got from Cel Press and Nature Databases. Finaly, 28 articles were chosen in result analysis. RESULTS AND CONCLUSION: Safety problems of induced pluripotent stem cels are attracting more and more attentions. Immunogenicity, potential tumorigenicity and epigenetic variation are major risks for the clinical applications of induced pluripotent stem cels. Safety issues of induced pluripotent stem cels mainly come from the reprogramming process. The “integrating genetic manipulation” may lead to a greater risk of tumorigenicity than non-integrating operations. Epigenetic variations emerge in the reprogramming, which are mostly relative to “epigenetic memory” of reprogrammed cels.