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Graft-Versus-Host Disease

A preclinical acute GVHD mouse model based on chemotherapy conditioning and MHC-matched transplantation

Bone Marrow Transplantation volume 51, pages 410–417 (2016)Cite this article

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Abstract

Animal disease models have been criticized for lack of resemblance to human illnesses, hampering transfer of knowledge from preclinical research to clinical medicine. In the field of allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is standard practice to study GVHD in lethal TBI-based murine models. Frequently, MHC-mismatched donors are used in GVHD models. In contrast, in clinical allo-HSCT conditioning with chemotherapy (+/−TBI) is common and donors are often MHC-matched. Aiming at a more clinically oriented situation, we established and characterized a murine MHC-matched, minor histocompatibility antigen mismatched GVHD model (LP/J [H2kb]→C57BL/6 [H2kb]) using busulfan and cyclophosphamide conditioning. We found typical clinical and histological features of acute GVHD. T-cell infiltration, GVHD-specific damage and systemic inflammation were similar to observations made in patients after allo-HSCT. In survivors of acute GVHD, we found expansion of CD4+ T cells and the development of scleroderma-like chronic GVHD. The use of chemotherapy-based, minor histocompatibility antigen (miHA)-mismatched GVHD animal models may be a good option when studying clinically relevant questions in the field of allo-HSCT.

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (PE1450/3-1), the Deutsche Krebshilfe (110466), the Josè Carreras Leukämie-Stiftung (R11/04) and the Wilhelm Sander-Stiftung (2010.039.1). We thank J Mengwasser, S Westphal and S Cordes for scientific discussion and A Wilke and A McGearey for technical support.

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  1. Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Berlin, Germany

    K Riesner, M Kalupa, Y Shi & O Penack

  2. Institute for Pathology, Charité University Medicine, Berlin, Germany

    S Elezkurtaj

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Correspondence to O Penack.

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Riesner, K., Kalupa, M., Shi, Y. et al. A preclinical acute GVHD mouse model based on chemotherapy conditioning and MHC-matched transplantation. Bone Marrow Transplant 51, 410–417 (2016). https://doi.org/10.1038/bmt.2015.279

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