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• W2756893114 abstract "// Alexander Rühle 1, 2 , Ramon Lopez Perez 1, 2 , Christin Glowa 1, 2 , Klaus-Josef Weber 2, 3 , Anthony D. Ho 4 , Jürgen Debus 2, 3 , Rainer Saffrich 4 , Peter E. Huber 1, 2, 3 and Nils H. Nicolay 1, 2, 3 1 Department of Molecular and Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany 2 Heidelberg Institute for Radiation Oncology (HIRO), National Center for Radiation Research in Oncology, 69120 Heidelberg, Germany 3 Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany 4 Department of Hematology and Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany Correspondence to: Nils H. Nicolay, email: n.nicolay@dkfz.de Keywords: mesenchymal stem cells, cisplatin, radiotherapy, DNA double-strand breaks, radiosensitization Received: July 19, 2017      Accepted: August 17, 2017      Published: September 23, 2017 ABSTRACT Cisplatin-based chemo-radiotherapy is widely used to treat cancers with often severe therapy-associated late toxicities. While mesenchymal stem cells (MSCs) were shown to aid regeneration of cisplatin- or radiation-induced tissue lesions, the effect of the combined treatment on the stem cells remains unknown. Here we demonstrate that cisplatin treatment radiosensitized human bone marrow-derived MSCs in a dose-dependent manner and increased levels of radiation-induced apoptosis. However, the defining stem cell properties of MSCs remained largely intact after cisplatin-based chemo-radiation, and stem cell motility, adhesion, surface marker expression and the characteristic differentiation potential were not significantly influenced. The increased cisplatin-mediated radiosensitivity was associated with a cell cycle shift of MSCs towards the radiosensitive G2/M phase and increased residual DNA double-strand breaks. These data demonstrate for the first time a dose-dependent radiosensitization effect of MSCs by cisplatin. Clinically, the observed increase in radiation sensitivity and subsequent loss of regenerative MSCs may contribute to the often severe late toxicities observed after cisplatin-based chemo-radiotherapy in cancer patients." @default.
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• W2756893114 date "2017-09-23" @default.
• W2756893114 modified "2023-10-18" @default.
• W2756893114 title "Cisplatin radiosensitizes radioresistant human mesenchymal stem cells" @default.
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• W2756893114 doi "https://doi.org/10.18632/oncotarget.21214" @default.
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