title: Metformin limits the tumourigenicity of iPS cells without affecting their pluripotency.
abstract: The antidiabetic drug metformin efficiently circumvents the dilemma that in reducing the tumourigenicity of stem cells, their essence, specifically their pluripotency, must also be sacrificed. Metformin prevents the occurrence or drastically reduces the size and weight of teratoma-like masses after the transplantation of induced pluripotent stem (iPS) cells into immunodeficient mice. Yet, iPS cells implanted into metformin-treated mice retain full pluripotency, as they produce the same number of distinct tissue types derived from the three embryonic germ layers that is observed in untreated mice. Mechanistically, metformin appears to suppress the Oct4-driven compartment of malignant stem cells responsible for teratocarcinoma growth while safeguarding an intact, Oct4-independent competency to generate terminally differentiated tissues. Metformin's ability to efficiently and specifically control the tumourigenic fate of teratoma-initiating iPS cells without interfering with their pluripotency not only has implications for the clinical use of iPS cells but also in stem cell biology, cancer and ageing.
authors.affiliation: Metabolism & Cancer Group, Translational Research Laboratory, Catalan Institute of Oncology, Girona, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vazquez-Martin
authors.forename: Sílvia
authors.initials: S
authors.lastname: Cufi
authors.forename: Eugeni
authors.initials: E
authors.lastname: Lopez-Bonet
authors.forename: Bruna
authors.initials: B
authors.lastname: Corominas-Faja
authors.forename: Cristina
authors.initials: C
authors.lastname: Oliveras-Ferraros
authors.forename: Begoña
authors.initials: B
authors.lastname: Martin-Castillo
authors.forename: Javier A
authors.initials: JA
authors.lastname: Menendez
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D013724:Teratoma / Q000378:metabolism / Q000473:pathology
chemical_list: D007004:Hypoglycemic Agents; D050814:Octamer Transcription Factor-3; D008687:Metformin