title: TRPV-1-mediated elimination of residual iPS cells in bioengineered cardiac cell sheet tissues.
abstract: The development of a suitable strategy for eliminating remaining undifferentiated cells is indispensable for the use of human-induced pluripotent stem (iPS) cell-derived cells in regenerative medicine. Here, we show for the first time that TRPV-1 activation through transient culture at 42 °C in combination with agonists is a simple and useful strategy to eliminate iPS cells from bioengineered cardiac cell sheet tissues. When human iPS cells were cultured at 42 °C, almost all cells disappeared by 48 hours through apoptosis. However, iPS cell-derived cardiomyocytes and fibroblasts maintained transcriptional and protein expression levels, and cardiac cell sheets were fabricated after reducing the temperature. TRPV-1 expression in iPS cells was upregulated at 42 °C, and iPS cell death at 42 °C was TRPV-1-dependent. Furthermore, TRPV-1 activation through thermal or agonist treatment eliminated iPS cells in cardiac tissues for a final concentration of 0.4% iPS cell contamination. These findings suggest that the difference in tolerance to TRPV-1 activation between iPS cells and iPS cell-derived cardiac cells could be exploited to eliminate remaining iPS cells in bioengineered cell sheet tissues, which will further reduce the risk of tumour formation.
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.|Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Matsuura
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.|Department of Cardiovascular Surgery, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Seta
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Haraguchi
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.
authors.forename: Khaled
authors.initials: K
authors.lastname: Alsayegh
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Sekine
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Hagiwara
authors.affiliation: Department of Cardiovascular Surgery, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D050916:TRPV Cation Channels; C494482:TRPV1 protein, human