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- W2003167114 abstract "The radiobiology of induced pluripotent stem cells (iPSC) compared to fibroblast progenitors has not been reported. An iPSC cell line was derived from a single individual's fibroblasts (FB) by transfection with 4 genes (OCT4, SOX2, NONOG and Lin28). We hypothesized that iPSCs would be radiosensitive relative to parental FB cells by reduced viability, increased apoptosis, depleted antioxidant stores and greater cell cycle arrest following irradiation. iPSCs and FB cells were irradiated to doses of 0, 0.5, 1.0, 1.5, 2.0 or 2.5 Gy at 600 mu/min using 6 MV photons. Viability was measured over 24 hr by trypan blue exclusion, percent of apoptotic cells by Annexin V and flow cytometer, cell cycle analysis by fixing cells with ice cold 70% ethanol for 24 hr, staining with propidium iodide and analyzing cells by Accun C-6 flow cytometer, and antioxidant stores by trolox-units in a commercial kit. Viability of iPSCs decreased significantly 24 hr following irradiation: 75.3 ± 3.9% at 0 Gy, 67.2 ± 2.4% after 0.5 Gy, 51.0 ± 6.1% following 1.0 Gy (p = 0.0010 compared to 0 Gy), 41.8 ± 3.3 after 1.5 Gy (p = 0.0010), 32.4 ± 5.2% after 2.0 Gy (p = 0.0009), and 32.3 ± 6.6% following 2.5 Gy (p = 0.0020). In contrast FB cells showed no viability loss after the same irradiation doses: 98.6 ± 0.3% at 0 Gy and 98.3 ± 0.4% following 2.5 Gy. iPSCs cells displayed significantly greater apoptosis: 13.6 ± 1.8% after 0 Gy, 16.1 ± 2.8% following 0.5 Gy, 33.5 ± 5.8% after 1.0 Gy (p = 0.0172 compared to 0 Gy), 35.7 ± 3.0% after 1.5 Gy (p = 0.0008), 50.3 ± 4.3% after 2.0 Gy (p = 0.0002) and 41.6 ± 6.9% following 2.5 Gy (p = 0.0078). In contrast, FB cells showed no significant apoptosis: 0 Gy, 0.6 ± 0.4% apoptotic cells, 0.7 ± 0.1% following 2.5 Gy. Antioxidant stores were higher in FB cells before irradiation compared to iPSC (0.051 ± 0.011, and 0.027 ± 0.002 trolox equivalents, respectively, p = 0.0197). However, one hour after 1 Gy, iPSC had higher levels of antioxidants than did FB cells (0.127 ± 0.001 and 0.043 ± 0.003, respectively, p < 0.0001). By 48 hrs FB antioxidant stores were greater than those in iPSCs (0.079 ± 0.011 and 0.0229 ± 0.013, respectively, p = 0.0319). There were no differences in cell cycle distribution in either cell phenotype after these irradiation doses. Human iPSCs are radiosensitive to doses of 0.5-2.5 Gy compared to their parental fibroblasts and may be a valuable platform for analysis of the radiobiologic effects of each of the transgenes inducing the iPSC phenotype." @default.
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- W2003167114 date "2014-09-01" @default.
- W2003167114 modified "2023-09-30" @default.
- W2003167114 title "Radiosensitivity of Human Induced Pluripotent Stem Cells Compared to Parental Fibroblasts" @default.
- W2003167114 doi "https://doi.org/10.1016/j.ijrobp.2014.05.2262" @default.
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