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Graft-versus-Host Disease

GVHD after chemotherapy conditioning in allogeneic transplanted mice

Bone Marrow Transplantation volume 42, pages 807–818 (2008)Cite this article

Abstract

GVHD is a major complication in allogeneic SCT. Available GVHD models are mainly based on radiotherapy-conditioning and/or immune deficient mice. GVHD models based on chemotherapy-based regimens remain poorly studied, despite 50% of all transplantations being chemotherapy based. Our aim was to develop a GVHD model using chemotherapy as conditioning. Female BALB/c (H-2Kd) were conditioned with BU–CY and transplanted with 2 × 107 BM and 3 × 107 spleen cells from either C57BL/6 (H-2 Kb) mice (allogeneic setting) or from male BALB/c to serve as a control group for regimen-related toxicity and engraftment. GVHD manifestations and histopathological changes were evaluated. Chimerism and donor T cells presence in skin, intestine and liver were studied using FACS-, FISH analysis and immunohistochemistry. Allogeneic transplanted mice developed lethal GVHD starting from day+7 with both histological and clinical signs. Donor T cells accumulated in recipient skin and intestine with GVHD progression. BM-failure, apoptosis and T-lymphocyte infiltration into target organs were significantly higher in allogeneic when compared with the syngeneic group. No toxicity or GVHD signs were observed in the syngeneic setting. We report a mouse model of GVHD using BU–CY conditioning that represents the most common myeloablative-conditioning regimen in clinical SCT. This model can be utilized to study the role of conditioning on mechanisms underlying GVHD.

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Acknowledgements

We thank The Swedish Cancer foundation ‘Cancer Fonden’ for the support provided for this investigation.

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Authors and Affiliations

  1. Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

    B Sadeghi, N Aghdami, Z Hassan, M Forouzanfar & M Hassan

  2. Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital-Huddinge, Stockholm, Sweden

    Z Hassan

  3. Morphology and Phenotype analysis, Institution for Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

    B Rozell

  4. Department of Biochemistry and Biophysics, Arrhenius Laboratories for the Natural Sciences, Stockholm University, Stockholm, Sweden

    M Abedi-Valugerdi

  5. Clinical Research Center, Karolinska University Hospital, Huddinge, Stockholm, Sweden

    M Hassan

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  1. B Sadeghi
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Correspondence to M Hassan.

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Sadeghi, B., Aghdami, N., Hassan, Z. et al. GVHD after chemotherapy conditioning in allogeneic transplanted mice. Bone Marrow Transplant 42, 807–818 (2008). https://doi.org/10.1038/bmt.2008.261

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