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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We thank The Swedish Cancer foundation ‘Cancer Fonden’ for the support provided for this investigation.
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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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DOI: https://doi.org/10.1038/bmt.2008.261
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