title: Suicide gene-mediated ablation of tumor-initiating mouse pluripotent stem cells.
abstract: Pluripotent stem cells, including embryonic stem (ES) and induced pluripotent stem (iPS) cells, serve as unlimited resources for cell replacement therapy and tissue engineering because such cells are capable of extensive proliferation in vitro and can give rise to lineages that represent any of the three embryonic germ layers. However, in the context of the in vivo behavior of cell transplants, key challenges need to be addressed and essential strategies should be developed before stem cells can be used in clinical practice. In the present study, we modified mouse ES/iPS cells to contain a suicide gene, deltaTK or CodA, under the transcriptional control of the EF1α or Nanog promoter. The suicide gene was introduced via lentivirus transduction without interfering with their self-renewal and pluripotency characteristics. We found that EF1α promoter-controlled deltaTK/CodA expression efficiently eliminated pluripotent stem cells and their derivatives both in vitro and in vivo. When the suicide gene was under the control of the Nanog promoter, tumor-initiating undifferentiated pluripotent stem cells were selectively ablated in vitro after prodrug treatment. These results indicate that modification of pluripotent stem cells with a suicide gene prior to transplantation offers a safe manner by which wayward stem cells, and their progeny, can be controlled in vivo. Our approach will render the clinical application of human pluripotent stem cells increasingly possible.
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong 510080, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Cai
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yuan
authors.forename: Fuyi
authors.initials: F
authors.lastname: Cheng
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Meihua
authors.initials: M
authors.lastname: Jiang
authors.forename: Yijia
authors.initials: Y
authors.lastname: Zhou
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Lahn
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Li
authors.forename: Andy Peng
authors.initials: AP
authors.lastname: Xiang
mesh_terms: D000818:Animals; D001483:Base Sequence; D016923:Cell Death; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D051379:Mice; D009369:Neoplasms / Q000473:pathology*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers