title: Characterizing the radioresponse of pluripotent and multipotent human stem cells.
abstract: The potential capability of stem cells to restore functionality to diseased or aged tissues has prompted a surge of research, but much work remains to elucidate the response of these cells to genotoxic agents. To more fully understand the impact of irradiation on different stem cell types, the present study has analyzed the radioresponse of human pluripotent and multipotent stem cells. Human embryonic stem (ES) cells, human induced pluripotent (iPS) cells, and iPS-derived human neural stem cells (iPS-hNSCs) cells were irradiated and analyzed for cell survival parameters, differentiation, DNA damage and repair and oxidative stress at various times after exposure. While irradiation led to dose-dependent reductions in survival, the fraction of surviving cells exhibited dose-dependent increases in metabolic activity. Irradiation did not preclude germ layer commitment of ES cells, but did promote neuronal differentiation. ES cells subjected to irradiation exhibited early apoptosis and inhibition of cell cycle progression, but otherwise showed normal repair of DNA double-strand breaks. Cells surviving irradiation also showed acute and persistent increases in reactive oxygen and nitrogen species that were significant at nearly all post-irradiation times analyzed. We suggest that stem cells alter their redox homeostasis to adapt to adverse conditions and that radiation-induced oxidative stress plays a role in regulating the function and fate of stem cells within tissues compromised by radiation injury.
authors.affiliation: Department of Radiation Oncology, University of California Irvine, Irvine, California, United States of America.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Lan
authors.forename: Munjal M
authors.initials: MM
authors.lastname: Acharya
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Tran
authors.forename: Jessica
authors.initials: J
authors.lastname: Bahari-Kashani
authors.forename: Neal H
authors.initials: NH
authors.lastname: Patel
authors.forename: Jan
authors.initials: J
authors.lastname: Strnadel
authors.forename: Erich
authors.initials: E
authors.lastname: Giedzinski
authors.forename: Charles L
authors.initials: CL
authors.lastname: Limoli
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D004249:DNA Damage; D004260:DNA Repair; D053595:Embryonic Stem Cells / Q000528:radiation effects*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000528:radiation effects*; D007700:Kinetics; D058953:Neural Stem Cells / Q000166:cytology / Q000528:radiation effects*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors