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Radiosensitivity of Human Inducible Pluripotential Stem Cells (iPSCs)
Author(s) -
Greenberger Joel S.,
Houghton Frank D.,
Zhang Xichen,
Nimgaonkar Vishwajit L.,
D'Aiuto Leonardo,
Epperly Michael W.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.530.1
Subject(s) - induced pluripotent stem cell , radiosensitivity , cell culture , sox2 , apoptosis , stem cell , microbiology and biotechnology , fibroblast , cell , cancer research , biology , chemistry , embryonic stem cell , medicine , biochemistry , radiation therapy , genetics , gene
Inducible human pluripotent stem cells, derived from fibroblasts, have been purposed for repair of tissue damage in various organs. iPSCs have displayed robust potential for providing reagent stem cells for tissue repair and regeneration. We evaluated the radiobiologic properties of a parent human fibroblast cell line and the iPSC derivative from plasmid transfection with OCT4, SOX2, NONOG and LIN28. We determined the radiosensitivity of iPSC cells compared to parental fibroblasts, and derivitive neural rosettes, prepared by growth of the iPSCs in 1% N2 supplement and bFGF. Cells of each cell type were irradiated to doses ranging from 0 to 2.5 Gy and the percent of apoptotic cells determined 24 or 48 hr after irradiation. The iPSC cells and rosettes were radiosensitive compared to fibroblasts: 43.6 ± 8.0 and 35.1 ± 3.9% apoptotic cells, respectively, compared to 1.9 ± 0.5% of fibroblasts cell at 24hrs after 2.5 Gy (p = 0.0261 and 0.0146, respectively). By 48 hr after irradiation, after significant cell loss, remaining iPSCs showed 18.0 ± 4.1 apoptosis compared to 7.1 ± 3.9% for fibroblasts and 30.9 ± 1.7% for rosettes. Five days after 2.5 Gy irradiation iPSCs showed a 98.5% decrease in cell number compared to 78% for fibroblasts (p = 0.0174). Elucidation of the mechanism of radiosensitivity of iPSCs may reveal a specific role for expression of one or more of the 4 transgene products in the parental fibroblast cell line. Supported by NIAID /NIH grant U191A168021–01 from NIAID