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@ARTICLE{Rhle:177187,
      author       = {A. Rühle$^*$ and D. Ping$^*$ and R. Lopez Perez$^*$ and M.
                      Strack$^*$ and S. Brons and Q. Yijia and J. Debus and P.
                      Wuchter and A.-L. Grosu$^*$ and P. E. Huber$^*$ and N.
                      Nicolay$^*$},
      title        = {{H}uman mesenchymal stromal cells maintain their stem cell
                      traits after high-{LET} particle irradiation - {P}otential
                      implications for particle radiotherapy and manned space
                      missions.},
      journal      = {Cancer letters},
      volume       = {524},
      issn         = {0304-3835},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2021-02321},
      pages        = {172 - 181},
      year         = {2021},
      note         = {#EA:E055#LA:E055#},
      abstract     = {The influence of high-linear energy transfer (LET) particle
                      radiation on the functionalities of mesenchymal stromal
                      cells (MSCs) is largely unknown. Here, we analyzed the
                      effects of proton (1H), helium (4He), carbon (12C) and
                      oxygen (16O) ions on human bone marrow-MSCs. Cell cycle
                      distribution and apoptosis induction were examined by flow
                      cytometry, and DNA damage was quantified using γH2AX
                      immunofluorescence and Western blots. Relative biological
                      effectiveness values of MSCs amounted to 1.0-1.1 for 1H,
                      1.7-2.3 for 4He, 2.9-3.4 for 12C and 2.6-3.3 for 16O.
                      Particle radiation did not alter the MSCs' characteristic
                      surface marker pattern, and MSCs maintained their
                      multi-lineage differentiation capabilities. Apoptosis rates
                      ranged low for all radiation modalities. At 24 h after
                      irradiation, particle radiation-induced ATM and CHK2
                      phosphorylation as well as γH2AX foci numbers returned to
                      baseline levels. The resistance of human MSCs to high-LET
                      irradiation suggests that MSCs remain functional after
                      exposure to moderate doses of particle radiation as seen in
                      normal tissues after particle radiotherapy or during manned
                      space flights. In the future, in vivo models focusing on
                      long-term consequences of particle irradiation on the bone
                      marrow niche and MSCs are needed.},
      keywords     = {Carbon ions (Other) / Helium ions (Other) / High-LET
                      radiation (Other) / Mesenchymal stem cells (Other) / Oxygen
                      ions (Other) / Particle radiotherapy (Other) / Proton
                      radiotherapy (Other) / Radiotherapy (Other) / Space
                      radiation (Other)},
      cin          = {E055 / FR01},
      ddc          = {570},
      cid          = {I:(DE-He78)E055-20160331 / I:(DE-He78)FR01-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34688844},
      doi          = {10.1016/j.canlet.2021.10.015},
      url          = {https://inrepo02.dkfz.de/record/177187},
}