The propensity for tumorigenesis in human induced pluripotent stem cells is related with 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.
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
Yi
Y
Liang
Hui
H
Zhang
Qi-Sheng
QS
Feng
Man-Bo
MB
Cai
Wen
W
Deng
Dajiang
D
Qin
Jing-Ping
JP
Yun
George Sai Wah
GS
Tsao
Tiebang
T
Kang
Miguel Angel
MA
Esteban
Duanqing
D
Pei
Yi-Xin
YX
Zeng
D000818:Animals; D063646:Carcinogenesis; D002478:Cells, Cultured; D056915:DNA Copy Number Variations; D042822:Genomic Instability; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D051379:Mice; D016513:Mice, SCID; D041681:NIH 3T3 Cells; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D018243:Teratocarcinoma / Q000209:etiology; D013724:Teratoma / Q000209:etiology*; D014410:Tumor Stem Cell Assay
D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse