GVHD after chemotherapy conditioning in allogeneic transplanted mice
GVHD after chemotherapy conditioning in allogeneic transplanted mice
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DOI：
10.1038/bmt.2008.261
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发表时间：
2008-12-01
影响因子：
4.8
通讯作者：
Hassan, M.
中科院分区：
文献类型：
--
作者：
Sadeghi, B.;Aghdami, N.;Hassan, M.
GVHD是异基因SCT的主要并发症。可用的GVHD模型主要基于放射治疗调节和/或免疫缺陷小鼠。基于化疗方案的GVHD模型研究仍然很少，尽管50%的移植是基于化疗的。我们的目的是建立一个GVHD模型，使用化疗作为条件。用BU-CY调节雌性BALB/c（H-2Kd），并移植来自C57 BL/6（H-2Kb）小鼠（同种异体设置）或来自雄性BALB/c的2 x 10（7）BM和3 x 10（7）脾细胞，作为方案相关毒性和植入的对照组。观察移植物抗宿主病（GVHD）表现及组织病理学改变。嵌合体和供体T细胞存在于皮肤，肠和肝脏进行了研究，使用流式细胞仪，荧光原位杂交分析和免疫组化。同种异体移植的小鼠从第+7天开始出现致死性GVHD，具有组织学和临床体征。随着GVHD进展，供体T细胞在受体皮肤和肠道中积累。与同基因组相比，异基因组的BM衰竭、细胞凋亡和T淋巴细胞浸润靶器官的情况明显增多。在同系环境中未观察到毒性或GVHD体征。我们报告了一个小鼠模型的GVHD使用BU-CY预处理，代表最常见的骨髓清除预处理方案在临床SCT。该模型可用于研究条件反射对GVHD机制的作用。
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.