シミズ　タツヤ   Shimizu Tatsuya   清水　達也    所属   医学研究科 医学研究科 (医学部医学科をご参照ください)    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Induced Pluripotent Stem Cell Elimination in a Cell Sheet by Methionine-Free and 42°C Condition for Tumor Prevention.
掲載誌名	正式名：Tissue engineering. Part C, Methods 略　 称：Tissue Eng Part C Methods ISSNコード：1937-3384/1937-3392
掲載区分	国外
出版社	Mary Ann Liebert, Inc.
巻・号・頁	24(10),pp.605-615
著者・共著者	MATSUURA Katsuhisa†*, ITO Kyoji, SHIRAKI Noubuaki, KUME Shoen, HAGIWARA Nobuhisa, SHIMIZU Tatsuya
担当区分	最終著者
発行年月	2018/10
概要	Pluripotent stem cells, including induced pluripotent stem (iPS) cells, are promising cell sources for regenerative medicine to replace injured tissues, and tissue engineering technologies enable engraftment of functional iPS cell-derived cells in vivo for prolonged periods. However, the risk of tumor formation is a concern for the use of iPS cells. Bioengineered tissues provide a suitable environment for cell survival, which requires vigorous efforts to eliminate remaining iPS cells and prevent tumor formation. We recently reported three iPS cell elimination strategies, including methionine-free medium, TRPV1 activation through 42°C cultivation, and dinaciclib, a cyclin-dependent kinase 1/9 inhibitor. However, it remains unclear how many iPS cells in bioengineered tissues can be eliminated using these strategies alone or in combination, as well as the mode of subsequent tumor prevention. In the present study, we found that 2 days of cultivation at 42°C sufficiently eliminated 1 × 102 iPS cells in fibroblast sheets and prevented tumor formation. After screening for suitable combinations of these strategies based on Lin28 expression in co-cultures of fibroblasts and 1 × 104 iPS cells, we found that 1 day of cultivation at 42°C in methionine-free culture medium with or without dinaciclib remarkably decreased Lin28 expression and prevented tumor formation. Furthermore, these culture strategies did not affect spontaneous beating or the cell number of human iPS cell-derived cardiomyocytes. These quantitative findings may contribute to decreasing tumor formation risk and development of regenerative medicine using iPS cells.
DOI	10.1089/ten.TEC.2018.0228
PMID	30234460