A novel mouse model of acute graft-versus-host disease based on chemotherapy conditioning and G-CSF mobilized graft.,Bone Marrow Transplantation

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A novel mouse model of acute graft-versus-host disease based on chemotherapy conditioning and G-CSF mobilized graft.
Bone Marrow Transplantation ( IF 4.5 ) Pub Date : 2019-09-26 , DOI: 10.1038/s41409-019-0700-4
Yishan Ye _{1,

2} , Laure Ricard ₁ , Nicolas Stocker ₁ , Mohamad Mohty _{1,

3} , Béatrice Gaugler ₁ , Florent Malard _{1,

3}

Affiliation

Acute graft-versus-host disease (aGVHD) is an important complication of allogeneic hematopoietic cell transplantation (HCT). The majority of aGVHD mouse models are based on radiation conditioning and bone marrow as graft, despite that most allo-HCTs performed now in clinic are based on chemotherapy conditioning and G-CSF mobilized graft. Aiming for a higher translational value, we constructed an MHC major mismatched [C57BL/6 (H-2 Kb) to BALB/c (H-2Kd)] aGVHD mouse model based on busulfan/cyclophosphomide (BU-CY) conditioning and human G-CSF mobilized splenocytes as graft. Allogeneic transplanted mice showed quick and profound donor engraftment. Moreover, there were quick onset (day +7) of typical clinical and histopathological signs of aGVHD, which gradually developed to extensive aGVHD. In addition, CD8+ T cells were the main aGVHD contributing T-cell subtype. No toxicity or GVHD signs were observed in the syngeneic setting. This clinical-relevant model offers a promising platform for future studies on aGVHD.

中文翻译：

基于化疗条件和G-CSF动员移植物的急性移植物抗宿主病小鼠模型。

急性移植物抗宿主病（aGVHD）是同种异体造血细胞移植（HCT）的重要并发症。尽管目前临床上执行的大多数同种异体HCT均基于化学疗法和G-CSF动员的移植物，但大多数aGVHD小鼠模型均基于放射调节和骨髓作为移植物。为了获得更高的翻译价值，我们基于环丁砜/环磷酰胺（BU-CY）调节条件和人G，构建了MHC主要错配[C57BL / 6（H-2 Kb）与BALB / c（H-2Kd）] aGVHD小鼠模型-CSF动员脾细胞作为移植物。同种异体移植小鼠表现出快速而深刻的供体植入。而且，出现典型的aGVHD临床和组织病理学症状的发病快（第7天），并逐渐发展为广泛的aGVHD。此外，CD8 + T细胞是主要的aGVHD贡献T细胞亚型。在同系环境中未观察到毒性或GVHD征象。这种与临床相关的模型为将来的aGVHD研究提供了有希望的平台。

更新日期：2019-09-26

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