Durante, M.

Hessel, P.

Luft, S.

Ritter, S.

Schroeder, I.

GSI Repository

Human embryonic stem cells: an ideal model for the risk assessment ofionizing radiation during early embryo development ∗I. Schroeder1, S. Luft†1, P. Hessel1, M. Durante1,2, and S. Ritter‡11GSI, Darmstadt, Germany; 2Technische Universita¨t Darmstadt, GermanyDiagnostic and/or therapeutic procedures that are basedon ionizing radiation are being increasingly used. How-ever, these procedures as well as the exposure to environ-mental radiation pose a threat to the early embryo possiblyleading to prenatal death, growth retardation, organ malfor-mation, mental retardation or childhood cancer [1]. Thus,a thorough risk assessment of radiation effects is manda-tory in situations of inevitable or unintended exposure ofthe conceptus in utero. Data about the biological effectsof a radiation exposure during the earliest stages of hu-man development are scarce predominately stemming fromatomic bomb survivors or observations made after fall-outs (e.g. Chernobyl). However, human embryonic stem(hES) cells that are derived from the inner cell mass ofthe blastocyst during embryo development present a valu-able tool to examine the radiation effects on early embryo-genesis. Apart from their indefinite self-renewing capac-ity, hES cells are pluripotent thereby being able to dif-ferentiate in vitro into all cell types of the body deriv-ing from the three germ layers endoderm, ectoderm andmesoderm (Fig.1). Therefore, the effect of radiation onpluripotent embryonic cells and their respective progenycan be easily analyzed on a molecular level. This is ba-sis of the BMBF funded project “In vitro Untersuchungenzur Wirkung von dicht und du¨nn ionisierender Strahlungauf die fru¨he pra¨natale Entwicklung”, which is performedin cooperation with the Universities of Applied SciencesAschaffenburg and Albstadt-Sigmaringen.In Germany, the work with hES cells requires ethical ap-proval in accordance with the German Embryo ProtectionAct and the German Stem Cell Act and underlies certainrestrictions regarding the choice of cell lines and the pro-cedures used to study scientific questions. However, exam-ining the effects of ionizing irradiation on early human de-velopment was regarded a top-ranking scientific goal andapproval was granted to study the impact of ionizing ir-radiation. Yet, the initial GSI approval to use hES cellsonly comprised the analysis of cardiac differentiation witha limited number of hES cell lines. An amendment nowallows us to use more sophisticated differentiation proce-dures, more suitable cell lines and not only cardiac differ-entiation protocols but also neuronal and endodermal onesto cover the entire developmental spectrum. Thus proto-cols for the generation of endoderm from human WA09have been established (see GSI report S. Luft et al., 2013)∗Work supported by BMBF grant 02NUK025A.† S. Luft is supported by HGS-HIRe.‡ s.ritter@gsi.deas these cells later in development will give rise to lung,pancreas or liver. Likewise extra-embryonic endoderm dif-ferentiation is currently established as it provides signalingfor cardiac differentiation, which has been shown to be im-paired upon irradiation [2-3]. In summary, the hES cellbased approach will provide insight into the impact of ion-izing irradiation on human development and possibly cellregeneration.Figure 1: Human development can be mimicked by usinghuman embryonic stem (hES) cells. hES cells can be dif-ferentiated in vitro into cells of the mesoderm, endodermand ectoderm and their respective progeny. Likewise, theycan form extra-embryonic tissue such as extra-embryonicendoderm, which gives rise to the yolk sac that providesearly nourishment and serves as a circulatory system untilthe embryos internal circulation is established.References[1] McCollough CH et al., “Radiation exposure and pregnancy:When should we be concerned?”, RadioGraphics 2007, 27:909-918[2] Helm A, “Influence of high- and low-LET radiation on thecardiac differentiation of mouse embryonic stem cells”, Dis-sertation, 2013, Department of Biology, TU Darmstadt[3] Luft S et al., “Fate of D3 mouse embryonic stem cells ex-posed to X-rays or carbon ions”, Mutat Res. 2014, 760:56-63GSI SCIENTIFIC REPORT 2013 BIOPHYSICS-15doi:10.15120/GR-2014-1-BIOPHYSICS-15 217

Human embryonic stem cells: an ideal model for the risk assessment of ionizing radiation during early embryo development

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Human embryonic stem cells: an ideal model for the risk assessment of ionizing radiation during early embryo development

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