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Stem cell research for preventing radiation-induced developmental damage

Although ionizing radiation is known to cause cell damage and genetic modifications, its effects on embryonic development are still poorly understood. This is why Prof. Dr. Suzanne Kadereit from the Albstadt-Sigmaringen University of Applied Sciences is involved in a cooperative project that uses human embryonic stem cells for studying the effects of ionizing radiation on prenatal brain development. She heads up the only university of applied sciences research group in Germany that has a license for the use of these cells.

Prof. Dr. Suzanne Kadereit from Albstadt-Sigmaringen University develops cell models based on human embryonic stem cells. © BioLAGO

We are constantly exposed to ionizing radiation from artificial or natural sources, including cosmic radiation caused by high-energy particles from space and exposure to radiation used by diagnostic imaging techniques such as CT and X-ray radiography. This can be problematic as ionizing radiation can cause cell damage which in the worst cases can kill the affected cells or cause genetic changes in the surviving cells. Densely ionizing radiation is particularly dangerous as it damages biological molecules more frequently than thinly ionizing radiation at the same dosage levels.  

“In addition to the direct effect of ionization in biological molecules, radiation also exerts an indirect effect through the formation of free water radicals which damage DNA and proteins in particular. This in turn can lead to oxidative stress and a broad range of modifications in individual cells or in the whole organism,” explains Prof. Dr. Suzanne Kadereit from Albstadt-Sigmaringen University whose research is focused on the effects of ionizing radiation on early human brain development.

While the consequences of exposure to radiation on children and adults are well known, little is yet known about its effect on human prenatal development. Available data are mainly based on animal experiments and on epidemiological studies that showed that fertilized eggs are particularly sensitive to radiation prior to nidation, and that exposure to radiation can potentially kill the embryo. “In addition to having a lethal effect, ionizing radiation can also lead to changes in cell proliferation, genetic modifications and disturbances in signalling cascades and normal development,” says Kadereit.

Irradiation endangers embryonic development

The cooperative BMBF project called “In vitro studies on the effect of densely and thinly ionizing radiation on early prenatal development” focuses particularly on the above consequences. The project partners are Suzanne Kadereit, Dr. Sylvia Ritter from the GSI Helmholtz Centre for Heavy Ion Research GmbH and Prof. Dr.-Ing. Christiane Thielemann from Aschaffenburg University of Applied Sciences. This interdisciplinary project uses human embryonic stem cells to study differences in radiation quality and determine the radiation risk. The researchers use molecular, cell biological and electrophysiological methods for their investigations. The project runs for three years until the end of August 2016. 

The three work groups are each investigating different aspects of early embryonic development. Prof. Kadereit is specifically focused on brain development in embryos. “As the development of the nervous system is a rather complex process and depends on precise patterns of cellular and molecular processes, it is assumed that exposure of the embryo to radiation has a decisive effect on early brain development,” said Kadereit, explaining why the researchers are focusing on this particular topic. Kadereit has been chair of stem cell biology and basic processes in the life sciences at Albstadt-Sigmaringen University since September and heads up the first and only university of applied sciences research group that has a license to work with human embryonic stem cells. “Students on work placements are introduced to research involving induced pluripotent stem cells, so-called iPSCs. These stem cells, which can be generated from adult cells and are able to develop into every other cell type in the body, are increasingly used in the pharmaceutical industry for drug development. So we are hoping to be able to contribute to increasing application- and industry-oriented R&D with stem cells in Germany,” Kadereit says. 

Cell models for risk assessment

A neurosphere with outgrowing nerve cells can be used as a 3D model of neural differentiation. © Suzanne Kadereit

Using human stem cells, Kadereit has developed an in-vitro test system to study the effects of radiation on early brain development. In the model, the stem cells are first differentiated into early CNS progenitor cells, which is the first of many steps of prenatal brain development. “At this point, we treat cells with a dose of up to 2 Gray X-rays or ion radiation and study their further development,” explains Kadereit. 

After a short recovery phase, the cells are placed in suspension and cultured further as so-called neurospheres, i.e. spherical clusters of neural stem cells in which the precursor cells mature. “This is the step where we study cell viability and in particular the radiation-related changes in the expression of marker genes that are specific to prenatal brain development.” 

Although the project is still in its infancy, Kadereit’s initial experiments have already shown that the irradiation of neural precursor cells led to measurable changes. However, further experiments are needed to verify the initial results and produce additional data. “In future, we will not only focus on gene expression changes, but also on the effect of radiation on cellular composition, the organization of the cells in neurospheres as well as cellular processes that are affected by oxidative stress,” says Kadereit.

Overall, the project partners are hoping that their in vitro models will be able to capture the radiation-induced cellular damage very precisely, thus enabling them in the future to derive prophylactic measures from the models. “Ultimately, we hope that our research improves the risk assessment of radiation sources, thus contributing to the safety of unborn babies,” explains Kadereit.

Application-oriented top research for up-and-coming scientists

“Research projects and the direct transfer of results into teaching are an important part of the Biomedical Sciences programme’s successful concept,” says Kadereit. The university works hard to get master’s students involved in research, which it does by integrating them into third-party-funded research projects. Students can also do their PhD at Albstadt-Sigmaringen University. PhDs are offered in cooperation with the University of Konstanz. “The Biomedical Sciences programme concentrates on the development of systems that can help benefit sick people,” she says. The newly created stem cell biology professorship will expand the existing research programme that already covers subjects such as bioanalytics, expression analyses, cell culture systems, gene technology and immunological working methods.

Further information:
Prof. Dr. Suzanne Kadereit
Life Sciences Faculty
Albstadt-Sigmaringen University
Anton-Günther-Straße 51
72488 Sigmaringen
E-mail: Kadereit(at)hs-albsig.de

 

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/stem-cell-research-for-preventing-radiation-induced-developmental-damage