Effect of combined sublethal X-ray irradiation and cyclosporine A treatment in NOD scid gamma (NSG) mice

  • Walcher Lia
    Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig, Germany
  • Müller Claudia
    Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig, Germany
  • Hilger Nadja
    Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig, Germany Institute for Clinical Immunology, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany
  • Kretschmer Anna
    Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig, Germany
  • Stahl Lilly
    Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig, Germany
  • Wigge Simone
    Grünenthal GmbH, Zieglerstrasse 6, 52078 Aachen, Germany
  • Rengelshausen Jens
    Grünenthal GmbH, Zieglerstrasse 6, 52078 Aachen, Germany
  • Müller Anne M.
    Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig, Germany
  • Fricke Stephan
    Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig, Germany

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タイトル別名
  • Effect of combined sublethal X-ray irradiation and cyclosporine A treatment in NOD <i>scid</i> gamma (NSG) mice

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<p>Cyclosporine A (CsA) is used in hematopoietic stem cell transplantations (HSCT) to prevent graft-versus-host disease (GvHD). GvHD is the most severe side effect of allogeneic HSCT and efficient therapies are lacking. Mouse models are an essential tool for assessing potential new therapeutic strategies. Our aim is to mimic a clinical setting as close as possible using CsA treatment after sublethal irradiation in NSG mice and thereby evaluate the feasibility of this mouse model for GvHD studies. The effect of CsA (7.5 mg/kg body weight) on sublethally X-ray irradiated (2 Gy) and non-irradiated NSG mice was tested. CsA was administered orally every twelve hours for nine days. Animals irradiated and treated with CsA showed a shorter survival (n=3/10) than irradiated animals treated with NaCl (n=10/10). Furthermore, combined therapy resulted in severe weight loss (82 ± 6% of initial weight, n=7, day 8), with weight recovery after the CsA application was ceased. A high number of apoptotic events in the liver was observed in these mice (0.431 ± 0.371 apoptotic cells/cm2, n=2, compared to 0.027 ± 0.034 apoptotic cells/cm2, n=5, in the non-irradiated group). Other adverse effects, including a decrease in white blood cell counts were non-CsA-specific manifestations of irradiation. The combination of CsA treatment with irradiation has a hepatotoxic and lethal effect on NSG mice, whereas the treatment without irradiation is tolerated. Therefore, when using in vivo models of GvHD in NSG mice, a combined treatment with CsA and X-ray irradiation should be avoided or carefully evaluated.</p>

収録刊行物

  • Experimental Animals

    Experimental Animals 68 (1), 1-11, 2019

    公益社団法人 日本実験動物学会

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