The propensity for tumorigenesis in human induced pluripotent stem cells is related with genomic instability  

作　　者：Yi Liang Hui Zhang Qi-Sheng Feng Man-Bo Cai Wen Deng Dajiang Qin Jing-Ping Yun George Sai Wah Tsao Tiebang Kang Miguel Angel Esteban Duanqing Pei Yi-Xin Zeng 

机构地区：[1]State Key Laboratory of Oncology in South China [2]Department of Experimental Research [3]Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou [4]Department of Anatomy, The University of Hong Kong [5]Department of Pathology, Sun Yat-sen University Cancer Center

出　　处：《Chinese Journal of Cancer》2013年第4期205-212,共8页

基　　金：supported by grants from the Chinese National 973 Program (No.2006CB910104 and No.2010CB912201);the Chinese National 863 Program (No.2006AA02A404);the Guangdong Province-National Natural Science Foundation of China Cooperation Program (No.u0732005);Ministry of Education of China (the academic award for excellent doctoral student,2010)

摘　　要：The discovery of induced pluripotent stem cells (iPSCs) is a promising advancement in the field of regenerative medicine. Previous studies have indicated that the teratoma-forming propensity of iPSCs is variable; however, the relationship between tumorigenic potential and genomic instability in human iPSCs (HiPSCs) remains to be fully elucidated. Here, we evaluated the malignant potential of HiPSCs by using both colony formation assays and tumorigenicity tests. We demonstrated that HiPSCs formed tumorigenic colonies when grown in cancer cell culture medium and produced malignancies in immunodeficient mice. Furthermore, we analyzed genomic instability in HiPSCs using whole-genome copy number variation analysis and determined that the extent of genomic instability was related with both the cells′ propensity to form colonies and their potential for tumorigenesis. These findings indicate a risk for potential malignancy of HiPSCs derived from genomic instability and suggest that quality control tests, including comprehensive tumorigenicity assays and genomic integrity validation, should be rigorously executed before the clinical application of HiPSCs. In addition, HiPSCs should be generated through the use of combined factors or other approaches that decrease the likelihood of genomic instability.The discovery of induced pluripotent stem cells （iPSCs） is a promising advancement in the field of regenerative medicine. Previous studies have indicated that the teratoma-forming propensity of iPSCs is variable; however, the relationship between tumorigenic potential and genomic instability in human iPSCs （HiPSCs） remains to be fully elucidated. Here, we evaluated the malignant potential of HiPSCs by using both colony formation assays and tumorigenicity tests. We demonstrated that HiPSCs formed tumorigenic colonies when grown in cancer cell culture medium and produced malignancies in immunodeficient mice. Furthermore, we analyzed genomic instability in HiPSCs using whole-genome copy number variation analysis and determined that the extent of genomic instability was related with both the cells′ propensity to form colonies and their potential for tumorigenesis. These findings indicate a risk for potential malignancy of HiPSCs derived from genomic instability and suggest that quality control tests, including comprehensive tumorigenicity assays and genomic integrity validation, should be rigorously executed before the clinical application of HiPSCs. In addition, HiPSCs should be generated through the use of combined factors or other approaches that decrease the likelihood of genomic instability.

关 键 词：Autophagy  fusion oncoprotein  acute MYELOID LEUKEMIA 

分 类 号：R730.2[医药卫生—肿瘤]