title: Cartilage tissue engineering identifies abnormal human induced pluripotent stem cells.
abstract: Safety is the foremost issue in all human cell therapies, but human induced pluripotent stem cells (iPSCs) currently lack a useful safety indicator. Studies in chimeric mice have demonstrated that certain lines of iPSCs are tumorigenic; however a similar screen has not been developed for human iPSCs. Here, we show that in vitro cartilage tissue engineering is an excellent tool for screening human iPSC lines for tumorigenic potential. Although all human embryonic stem cells (ESCs) and most iPSC lines tested formed cartilage safely, certain human iPSCs displayed a pro-oncogenic state, as indicated by the presence of secretory tumors during cartilage differentiation in vitro. We observed five abnormal iPSC clones amoungst 21 lines derived from five different reprogramming methods using three cellular origins. We conclude that in vitro cartilage tissue engineering is a useful approach to identify abnormal human iPSC lines.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamashita
authors.forename: Shiying
authors.initials: S
authors.lastname: Liu
authors.forename: Knut
authors.initials: K
authors.lastname: Woltjen
authors.forename: Bradley
authors.initials: B
authors.lastname: Thomas
authors.forename: Guoliang
authors.initials: G
authors.lastname: Meng
authors.forename: Akitsu
authors.initials: A
authors.lastname: Hotta
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Takahashi
authors.forename: James
authors.initials: J
authors.lastname: Ellis
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamanaka
authors.forename: Derrick E
authors.initials: DE
authors.lastname: Rancourt
mesh_terms: D002356:Cartilage / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D023822:Tissue Engineering