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| 2. |
- Sadeghi, B., et al.
(författare)
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Early-phase GVHD gene expression profile in target versus non-target tissues : kidney, a possible target?
- 2013
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 48:2, s. 284-293
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Tidskriftsartikel (refereegranskat)abstract
- GVHD is a major complication after allo-SCT. In GVHD, some tissues like liver, intestine and skin are infiltrated by donor T cells while others like muscle are not. The mechanism underlying targeted tropism of donor T cells is not fully understood. In the present study, we aim to explore differences in gene expression profile among target versus non-target tissues in a mouse model of GVHD based on chemotherapy conditioning. Expression levels of JAK-signal transducers and activators of transcription (STAT), CXCL1, ICAM1 and STAT3 were increased in the liver and remained unchanged (or decreased) in the muscle and kidney after conditioning. At the start of GVHD the expression levels of CXCL9, ITGb2, SAA3, MARCO, TLR and VCAM1 were significantly higher in the liver or kidney compared with the muscle of GVHD animals. Moreover, biological processes of inflammatory reactions, leukocyte migration, response to bacterium and chemotaxis followed the same pattern. Our data show that both chemotherapy and allogenicity exclusively induce expression of inflammatory genes in target tissues. Moreover, gene expression profile and histopathological findings in the kidney are similar to those observed in the liver of GVHD mice. Bone Marrow Transplantation (2013) 48, 284-293; doi:10.1038/bmt.2012.120; published online 23 July 2012
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| 3. |
- Sadeghi, B., et al.
(författare)
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GVHD after chemotherapy conditioning in allogeneic transplanted mice
- 2008
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 42:12, s. 807-818
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Sadeghi, B., et al.
(författare)
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The effect of administration order of BU and CY on engraftment and toxicity in HSCT mouse model
- 2008
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 41:10, s. 895-904
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Tidskriftsartikel (refereegranskat)abstract
- Conditioning regimens are an important issue determining the outcome of hematopoietic stem cell transplantation (HSCT). Less toxicity, early engraftment and no relapse are the aims of efficient conditioning. Our objective was to investigate the long-term effects of BU-CY and their administration order on the toxicity and chimerism in a mouse model of HSCT. Female BALB/c mice were treated with either BU (15 mg/kg/day x 4)-CY (100 mg/kg/day x 2) or CY-BU. Treated mice were transplanted with Sca-1+ cells from male BALB/c mice. Until 90 days after HSCT, the animals were monitored for body weight and analyzed for cellular phenotype of the thymus, spleen and BM, total chimerism, the spleen chimerism of DCs and T regulatory (Treg) cells, and hepatotoxicity. BU-CY and CY-BU treatments exerted comparable myeloablative and immunosuppressive effects. The long-term engraftment of donor cells in the BM and thymus regeneration showed the same features in both groups. However, the two regimens differed; in general, hepatotoxicity and chimerism of DC and Treg cells. In the long term, BU-CY, but not CY-BU caused a marked decrease in body weight and a significant increase in the activities of the liver enzymes, particularly aspartate amino transferase (AST). We conclude that the alteration of the administration order of BU-CY to CY-BU not only gives the same level of engraftment but also reduces the toxicity of the conditioning regimen that might be valuable specially in young patients who are undergoing HSCT.
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| 5. |
- Smedler, Ann-Charlotte, et al.
(författare)
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Neuropsychological outcome in very young hematopoietic SCT recipients in relation to pretransplant conditioning
- 2008
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 42:8, s. 515-22
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Tidskriftsartikel (refereegranskat)abstract
- Stem cell transplantation involves conditioning with TBI and/or intensive chemotherapy, which may cause long-term neuropsychological deficits, particularly in children treated at a very young age. The aim of this study was to investigate whether very young children who receive chemotherapy-based conditioning only (BUCY) may have a more favorable neuropsychological outcome than children conditioned with TBI-CY. Twenty-two children who underwent allogeneic SCT at 0.4-3.6 years of age were subject to an extensive neuropsychological assessment at an average of 6.5 years post-therapy. The test results of 10 children exposed to BU were compared to the results of 12 children who had received TBI. Ten of them had received single-dose TBI, whereas two had received fractionated TBI. The BU group performed at age level on verbal measures, but tended to score below age level in the executive and visuo-spatial domains (P<0.01). By comparison, children treated with TBI had more pervasive neuropsychological impairments, including motor deficits (P<0.01) and varying degrees of perceptual (P<0.05), executive and cognitive (P<0.05) problems. In conclusion, children transplanted at a very young age had a more favorable neuropsychological development if conditioned with BUCY than if conditioned with single-dose TBI-CY.
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