RRC ID 45340
Author Kamada M, Mitsui Y, Kumazaki T, Kawahara Y, Matsuo T, Takahashi T.
Title Tumorigenic risk of human induced pluripotent stem cell explants cultured on mouse SNL76/7 feeder cells.
Journal Biochem Biophys Res Commun
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.
Volume 453(3)
Pages 668-73
Published 2014-10-24
DOI 10.1016/j.bbrc.2014.10.009
PII S0006-291X(14)01795-1
PMID 25305485
MeSH Animals Carcinogenesis* Cell Line Feeder Cells* Gene Expression Profiling Humans Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism Mice Mice, SCID Neoplasms, Experimental / pathology Stem Cell Transplantation
IF 2.705
Times Cited 5
Human and Animal Cells