Stem Cell Differentiation and Cytogenetics

Group leader: Dr. Sylvia Ritter

Stem cells play a pivotal role in tissue development and maintenance by replenishing cells lost due to physiological tissue turnover or due to damaging agents such as ionizing radiation. To fully understand the effects of X-ray and particle exposure on stem cells and the underlying molecular mechanisms the group utilizes several cell models: embryonic stem cells, which can give rise to all tissues of an organism (left panel), their progeny (e.g. neural stem cells, middle panel) as well as bone marrow stem cells. Parameters such as cell survival, marker expression, differentiation capacity and genetic stability (left panel) are examined at various times after exposure. Currently, the group focuses on the effects of radon that is offered for the treatment of rheumatic diseases, carbon-ions that are increasingly used in cancer therapy and Fe-ions that are relevant for space Research

 

GSI Helmholtzzentrum für Schwerionenforschung GmbH
https://www.gsi.de/fileadmin/Biophysik/Bilder/Research/Stem_Cell_Differentiation_and_Cytogenetics/Picture___Web_Stem_Cells_Group.jpg
Left: Colonies of human embryonic stem cells grown on mouse fibroblasts. Middle: Human neural stem cells immunostained for Nestin (green) and Sox2 (red). DNA was counterstained with DAPI (blue). Right: Karyotype of a human cell after heavy ion exposure revealed by mFISH technique. The cell harbors a complex aberration involving several chromosomes (red circle).
GSI Helmholtzzentrum für Schwerionenforschung GmbH

Main research topics

  • Radiation response of human embryonic stem cells and their progeny
    • Self-renewal
    • Differentiation/regeneration (neural cells, cardiomyocytes, endoderm cells)
    • Functionality
    • Genetic stability
  • Cytogenetic damage in hematopoietic stem and somatic cells
    • Effects of radon spa therapy (in vivo studies)
    • RBE of HZE-particles heavy ions (in vitro studies)

Collaborations

  • Helmholtz Zentrum München, Germany (Prof. M. Atkinson, Dr. S. Tapio)
  • University of Applied Sciences Aschaffenburg, Germany (Professor C. Thielemann)
  • Jagiellonian University, Krakov, Poland (Prof. E. Gudowska-Nowak)
  • Joint Institute for Nuclear Research, Dubna, Russia (Dr. E. Nasonova)
  • Technical University of Ilmenau, Germany (Prof. A. Schober)
  • Technical University of Darmstadt, Germany (Prof. B. Laube, Prof. M. Löbrich, Prof. G. Thiel)
  • Heidelberg University Hospital, Germany (Prof. J. Debus)

 

Funding

  • BMBF 02NUK049A (Verbundprojekt Brain Radiation Assay: Etablierung eines in vitro Systems zur Analyse und Prädiktion von Schäden im zentralen Nervensystem nach Exposition mit ionisierender Strahlung in Kombination mit anderen Neurotoxika)
  • BMBF 02NUK050A (Verbundprojekt GREWIS-alpha: Genetische Risiken und entzündungshemmende Wirkung von dicht-ionisierender alpha-Strahlung)
  • BMBF 02NUK034C (Verbundprojekt Neurorad: Ein Ansatz zur Bewertung neurologischer Strahlenschäden)
  • Bundesamt für Strahlenschutz, Strahlenresistenzmechanismen in Tumorstammzellen, Vorhaben 3616S32262
  • HGS-HIRE (Helmholtz Graduate School for Hadron and Ion Research)

Group members

  • Research scientists:
    Dr. Onetsine Arrizabalaga (Neural stem cells)
    Dr. Carola Hartel (Genetic risk of Radon)
    Dr. Insa Schröder (Stem cells and Differentiation)
  • Technicians:
    Emilia Choman
    Kim Sara Jung
    Dr. Yvonne Knies
  • PhD student:
    Kim Röder
    Celine Schielke
    Timo Smit

Selected publications

  • Nitsch S et al., Functional video-based analysis of 3D cardiac structures generated from human embryonic stem cells. Stem Cell Res.29, 115 (2018)
  • Deperas-Standylo J.et al, Production and distribution of aberrations in resting or cycling human lymphocytes following Fe-ion or Cr-ion irradiation: Emphasis on single track effects. Adv. Space Res.50, 584 (2012)Hartel C et al., Chromosomal aberrations in peripheral blood lymphocytes of prostate cancer patients treated with IMRT and carbon ions. Radiother Oncol.95, 73 (2010)
  • Helm A et al., Ionizing radiation impacts on cardiac differentiation of mouse embryonic stem cells. Stem Cells Dev. 25, 178 (2016)
  • Helm A et al., The influence of C-Ions and X-rays on human umbilical vein endothelial cells. Front Oncol. 6(2016)
  • Lee R et al., Chromosome aberration measurements in mitotic and G2-PCC lymphocytes at the standard sampling time of 48 h underestimate the effectiveness of high-LET particles.  Radiat Environ Biophys 50, 371 (2011)
  • Luft S et al., Fate of D3 mouse embryonic stem cells exposed to X-rays or carbon ions. Mutat Res Genet Toxicol Environ Mutagen760, 56 (2014)
  • Luft S et al., Ionizing radiation alters human embryonic stem cell properties and differentiation capacity by diminishing the expression of activin receptors. Stem Cells Dev. 26, 341 (2017)
  • Mayer M et al., Electrophysiological investigation of human embryonic stem cell derived neurospheres using a novel spike detection algorithm. Biosens. Bioelectron. 100, 462 (2018)
  • Ritter S and Durante M, Heavy-ion induced chromosomal aberrations: a review. Mutat Res14, 701, 38 (2010)