title: Comparison of the early response of human embryonic stem cells and human induced pluripotent stem cells to ionizing radiation.
abstract: Despite the well-demonstrated efficacy of stem cell (SC) therapy, this approach has a number of key drawbacks. One important concern is the response of pluripotent SCs to treatment with ionizing radiation (IR), given that SCs used in regenerative medicine will eventually be exposed to IR for diagnostic or treatment‑associated purposes. Therefore, the aim of the present study was to examine and compare early IR‑induced responses of pluripotent SCs to assess their radioresistance and radiosensitivity. In the present study, 3 cell lines; human embryonic SCs (hESCs), human induced pluripotent SCs (hiPSCs) and primary human dermal fibroblasts (PHDFs); were exposed to IR at doses ranging from 0 to 15 gray (Gy). Double strand breaks (DSBs), and the gene expression of the following DNA repair genes were analyzed: P53; RAD51; BRCA2; PRKDC; and XRCC4. hiPSCs demonstrated greater radioresistance, as fewer DSBs were identified, compared with hESCs. Both pluripotent SC lines exhibited distinct gene expression profiles in the most common DNA repair genes that are involved in homologous recombination, non‑homologous end‑joining and enhanced DNA damage response following IR exposure. Although hESCs and hiPSCs are equivalent in terms of capacity for pluripotency and differentiation into 3 germ layers, the results of the present study indicate that these 2 types of SCs differ in gene expression following exposure to IR. Consequently, further research is required to determine whether hiPSCs and hESCs are equally safe for application in clinical practice. The present study contributes to a greater understanding of DNA damage response (DDR) mechanisms activated in pluripotent SCs and may aid in the future development of safe SC‑based clinical protocols.
authors.affiliation: Radiobiology Laboratory, Greater Poland Cancer Centre, 61‑866 Poznan, Poland.
authors.forename: Wiktoria Maria
authors.initials: WM
authors.lastname: Suchorska
authors.affiliation: Radiobiology Laboratory, Greater Poland Cancer Centre, 61‑866 Poznan, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Augustyniak
authors.affiliation: Radiobiology Laboratory, Greater Poland Cancer Centre, 61‑866 Poznan, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Łukjanow
mesh_terms: D024682:BRCA2 Protein / Q000235:genetics; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D051747:DNA-Activated Protein Kinase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000528:radiation effects; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D009687:Nuclear Proteins / Q000235:genetics; D051135:Rad51 Recombinase / Q000235:genetics; D011839:Radiation, Ionizing; D059467:Transcriptome / Q000528:radiation effects*
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C101467:XRCC4 protein, human; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D051135:Rad51 Recombinase