title: Tumorigenic risk of human induced pluripotent stem cell explants cultured on mouse SNL76/7 feeder cells.
abstract: The potential for tumor formation from transplanted human induced pluripotent stem cell (hiPSC) derivatives represents a high risk in their application to regenerative medicine. We examined the genetic origin and characteristics of tumors, that were formed when 13 hiPSC lines, established by ourselves, and 201B7 hiPSC from Kyoto University were transplanted into severe combined immune-deficient (SCID) mice. Though teratomas formed in 58% of mice, five angiosarcomas, one malignant solitary fibrous tumor and one undifferentiated pleomorphic sarcoma formed in the remaining mice. Three malignant cell lines were established from the tumors, which were derived from mitomycin C (MMC)-treated SNL76/7 (MMC-SNL) feeder cells, as tumor development from fusion cells between MMC-SNL and hiPSCs was negative by genetic analysis. While parent SNL76/7 cells produced malignant tumors, neither MMC-SNL nor MMC-treated mouse embryo fibroblast (MEF) produced malignant tumors. When MMC-SNL feeder cells were co-cultured with hiPSCs, growing cell lines were generated, that expressed genes similar to the parent SNL76/7 cells. Thus, hiPSCs grown on MMC-SNL feeder cells have a high risk of generating feeder-derived malignant tumors. The possible mechanism(s) of growth restoration and the formation of multiple tumor types are discussed with respect of the interactions between MMC-SNL and hiPSC.
authors.affiliation: Laboratory of Physiological Chemistry, Faculty of Pharmaceutical Sciences at Kagawa, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan.
authors.forename: Mizuna
authors.initials: M
authors.lastname: Kamada
authors.affiliation: Laboratory of Physiological Chemistry, Faculty of Pharmaceutical Sciences at Kagawa, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan. Electronic address: y-mitsui8310@hb.tp1.jp.
authors.forename: Youji
authors.initials: Y
authors.lastname: Mitsui
authors.affiliation: Laboratory of Physiological Chemistry, Faculty of Pharmaceutical Sciences at Kagawa, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kumazaki
authors.affiliation: Laboratory of Physiological Chemistry, Faculty of Pharmaceutical Sciences at Kagawa, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kawahara
authors.affiliation: Laboratory of Physiological Chemistry, Faculty of Pharmaceutical Sciences at Kagawa, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan.
authors.forename: Taira
authors.initials: T
authors.lastname: Matsuo
authors.affiliation: Laboratory of Physiological Chemistry, Faculty of Pharmaceutical Sciences at Kagawa, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan. Electronic address: t-takahashi@kph.bunri-u.ac.jp.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D002460:Cell Line; D061252:Feeder Cells; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000473:pathology; D033581:Stem Cell Transplantation
keywords: Cell transplantation; Human iPS cells; SNL76/7 feeder cell; Tumor formation