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GVHD after chemotherapy conditioning in allogeneic transplanted mice
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- Sadeghi, B. (författare)
- Karolinska Institutet
- Aghdami, N. (författare)
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- Hassan, Z. (författare)
- Karolinska Institutet
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- Forouzanfar, M. (författare)
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- (creator_code:org_t)
- 2008-09-29
- 2008
- Engelska.
- Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 42:12, s. 807-818
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- BU
- CY
- chemotherapy conditioning
- GVHD
- mouse model
- hematopoietic stem cell transplantation
- versus-host-disease
- bone-marrow-transplantation
- total-body irradiation
- minor histocompatibility antigens
- stem-cell transplantation
- acute myeloid-leukemia
- t-cells
- in-vivo
- randomized-trial
- lethal graft
- NATURAL SCIENCES
- NATURVETENSKAP
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- art (ämneskategori)
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- Sadeghi, B.
- Aghdami, N.
- Hassan, Z.
- Forouzanfar, M.
- Rozell, B.
- Abedi-Valugerdi, ...
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- Hassan, M.
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