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@ARTICLE{Strack:291120,
      author       = {M. Strack$^*$ and J. Kückelhaus and M. Diebold and P.
                      Wuchter and P. E. Huber and O. Schnell and R. Sankowski and
                      M. Prinz and A.-L. Grosu$^*$ and D. H. Heiland and N. H.
                      Nicolay$^*$ and A. Rühle$^*$},
      title        = {{E}ffects of tumor treating fields ({TTF}ields) on human
                      mesenchymal stromal cells.},
      journal      = {Journal of neuro-oncology},
      volume       = {169},
      number       = {2},
      issn         = {0167-594X},
      address      = {Dordrecht [u.a.]},
      publisher    = {Springer Science + Business Media B.V},
      reportid     = {DKFZ-2024-01323},
      pages        = {329-340},
      year         = {2024},
      note         = {#LA:E055# / 2024 Sep;169(2):329-340},
      abstract     = {Mesenchymal stromal cells (MSCs) within the glioblastoma
                      microenvironment have been shown to promote tumor
                      progression. Tumor Treating Fields (TTFields) are
                      alternating electric fields with low intensity and
                      intermediate frequency that exhibit anti-tumorigenic
                      effects. While the effects of TTFields on glioblastoma cells
                      have been studied previously, nothing is known about the
                      influence of TTFields on MSCs.Single-cell RNA sequencing and
                      immunofluorescence staining were employed to identify
                      glioblastoma-associated MSCs in patient samples.
                      Proliferation and clonogenic survival of human bone
                      marrow-derived MSCs were assessed after TTFields in vitro.
                      MSC' characteristic surface marker expression was determined
                      using flow cytometry, while multi-lineage differentiation
                      potential was examined with immunohistochemistry. Apoptosis
                      was quantified based on caspase-3 and annexin-V/7-AAD levels
                      in flow cytometry, and senescence was assessed with
                      ß-galactosidase staining. MSCs' migratory potential was
                      evaluated with Boyden chamber assays.Single-cell RNA
                      sequencing and immunofluorescence showed the presence of
                      glioblastoma-associated MSCs in patient samples. TTFields
                      significantly reduced proliferation and clonogenic survival
                      of human bone marrow-derived MSCs by up to $60\%$ and
                      $90\%,$ respectively. While the characteristic surface
                      marker expression and differentiation capacity were intact
                      after TTFields, treatment resulted in increased apoptosis
                      and senescence. Furthermore, TTFields significantly reduced
                      MSCs' migratory capacity.We could demonstrate the presence
                      of tumor-associated MSCs in glioblastoma patients, providing
                      a rationale to study the impact of TTFields on MSCs.
                      TTFields considerably increase apoptosis and senescence in
                      MSCs, resulting in impaired survival and migration. The
                      results provide a basis for further analyses on the role of
                      MSCs in glioblastoma patients receiving TTFields.},
      keywords     = {Glioma (Other) / Mesenchymal stem cells (Other) /
                      Mesenchymal stromal cells (Other) / Tumor microenvironment
                      (Other)},
      cin          = {FR01 / E055},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331 / I:(DE-He78)E055-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38900237},
      doi          = {10.1007/s11060-024-04740-0},
      url          = {https://inrepo02.dkfz.de/record/291120},
}