% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Rhle:180796,
      author       = {A. Rühle$^*$ and M. Lies$^*$ and M. Strack$^*$ and R. L.
                      Perez$^*$ and B. Bieber$^*$ and A. R. Thomsen$^*$ and P.
                      Bronsert and P. Huber$^*$ and J. Hess$^*$ and A. Knopf and
                      P. Wuchter and A.-L. Grosu$^*$ and N. Nicolay$^*$},
      title        = {{H}uman {M}esenchymal {S}tromal {C}ells {D}o {N}ot {C}ause
                      {R}adioprotection of {H}ead-and-{N}eck {S}quamous {C}ell
                      {C}arcinoma.},
      journal      = {International journal of molecular sciences},
      volume       = {23},
      number       = {14},
      issn         = {1422-0067},
      address      = {Basel},
      publisher    = {Molecular Diversity Preservation International},
      reportid     = {DKFZ-2022-01558},
      pages        = {7689},
      year         = {2022},
      note         = {#EA:E055#LA:E055#},
      abstract     = {Radiotherapy of head-and-neck squamous cell carcinoma
                      (HNSCC) can cause considerable normal tissue injuries, and
                      mesenchymal stromal cells (MSCs) have been shown to aid
                      regeneration of irradiation-damaged normal tissues. However,
                      utilization of MSC-based treatments for HNSCC patients
                      undergoing radiotherapy is hampered by concerns regarding
                      potential radioprotective effects. We therefore investigated
                      the influence of MSCs on the radiosensitivity of HNSCCs.
                      Several human papillomavirus (HPV)-negative and HPV-positive
                      HNSCCs were co-cultured with human bone marrow-derived MSCs
                      using two-dimensional and three-dimensional assays.
                      Clonogenic survival, proliferation, and viability of HNSCCs
                      after radiotherapy were assessed depending on MSC
                      co-culture. Flow cytometry analyses were conducted to
                      examine the influence of MSCs on irradiation-induced cell
                      cycle distribution and apoptosis induction in HNSCCs.
                      Immunofluorescence stainings of γH2AX were conducted to
                      determine the levels of residual irradiation-induced DNA
                      double-strand breaks. Levels of connective tissue growth
                      factor (CTGF), a multifunctional pro-tumorigenic cytokine,
                      were analyzed using enzyme-linked immunosorbent assays.
                      Neither direct MSC co-culture nor MSC-conditioned medium
                      exerted radioprotective effects on HNSCCs as determined by
                      clonogenic survival, proliferation, and viability assays.
                      Consistently, three-dimensional microwell arrays revealed no
                      radioprotective effects of MSCs. Irradiation resulted in a
                      G2/M arrest of HNSCCs at 96 h independently of MSC
                      co-culture. HNSCCs' apoptosis rates were increased by
                      irradiation irrespective of MSCs. Numbers of residual γH2AX
                      foci after irradiation with 2 or 8 Gy were comparable
                      between mono- and co-cultures. MSC mono-cultures and
                      HNSCC-MSC co-cultures exhibited comparable CTGF levels. We
                      did not detect radioprotective effects of human MSCs on
                      HNSCCs. Our results suggest that the usage of MSC-based
                      therapies for radiotherapy-related toxicities in HNSCC
                      patients may be safe in the context of absent
                      radioprotection.},
      keywords     = {co-culture (Other) / head-and-neck cancer (Other) /
                      head-and-neck squamous cell carcinoma (Other) / mesenchymal
                      stromal cells (Other) / radioresistance (Other) /
                      radiosensitivity (Other) / radiotherapy (Other)},
      cin          = {FR01 / E055 / E221},
      ddc          = {540},
      cid          = {I:(DE-He78)FR01-20160331 / I:(DE-He78)E055-20160331 /
                      I:(DE-He78)E221-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35887032},
      doi          = {10.3390/ijms23147689},
      url          = {https://inrepo02.dkfz.de/record/180796},
}