GVHD after chemotherapy conditioning in allogeneic transplanted mice

authorCount :7
GVHD is a major complication in allogeneic SCT. Available GVHD models are mainly based on radio-therapy-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 x 10(7) BM and 3 x 10(7) spleen cells from either C57BL/6 (H-2Kb) 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.

Aghdami, N. (author)
Hassan, Z.Karolinska Institutet (author)
Forouzanfar, M. (author)
Rozell, B.Karolinska Institutet (author)
Abedi-Valugerdi, ManuchehrKarolinska Institutet,Stockholms universitet,Institutionen för biokemi och biofysik(Swepub:su)mabed (author)
Hassan, M.Karolinska Institutet (author)
Karolinska InstitutetInstitutionen för biokemi och biofysik (creator_code:org_t)

In:Bone Marrow Transplantation: Springer Science and Business Media LLC42:12, s. 807-8180268-33691476-5365

By the author/editor: Sadeghi, B.; Aghdami, N.; Hassan, Z.; Forouzanfar, M.; Rozell, B.; Abedi-Valugerdi, ...; show more...; Hassan, M.; show less...

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