title: Residual undifferentiated cells during differentiation of induced pluripotent stem cells in vitro and in vivo.
abstract: Induced pluripotent stem (iPS) cells are a potential cell source for regenerative medicine. However, the tumorigenicity of iPS cells is a big concern for clinical application. In addition to the genetic manipulation of the reprogramming process and the greater risk of tumor formation, it is unclear whether iPS cells with normal development potential are still tumorigenic. Here, we investigated 3 mouse iPS cell lines, including one line that is able to generate full-term mice via tetraploid blastocyst complementation. We found that a small number of undifferentiated iPS cells could be steadily isolated and expanded after long-term differentiation of cells in vitro or in vivo. The residual undifferentiated iPS cells could be expanded and redifferentiated, and undifferentiated pluripotent stem cells could again be isolated after further rounds of differentiation, suggesting that residual undifferentiated iPS cells could not be eliminated by extended cell differentiation. The residual undifferentiated cells could form teratomas in vivo, indicating that they are a potential tumorigenic risk during transplantation. These findings prompt us to reconsider the strategies for solving the tumorigenic problem of iPS cells, not only focusing on improving the reprogramming process.
authors.affiliation: Shanghai Key Laboratory of Tissue Engineering, Department of Plastic and Reconstructive Surgery, National Tissue Engineering Center of China, Shanghai Jiao Tong University School of Medicine, Shanghai 9th People's Hospital, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fu
authors.forename: Shu Jun
authors.initials: SJ
authors.lastname: Wang
authors.forename: Guang Dong
authors.initials: GD
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yilin
authors.initials: Y
authors.lastname: Cao
authors.forename: Wen Jie
authors.initials: WJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation*; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D011003:Ploidies; D014184:Transplantation, Homologous