Impact of Mesenchymal stem cell transplantation in mouse GVHD model

间充质干细胞移植对小鼠 GVHD 模型的影响

基本信息

批准号：
18591195
负责人：
SUZUKI Nobuhiro
金额：
$ 2.48万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591195/
关键词：
Transplantation mesenchymal stem cell Graft versus host disease mouse model

项目摘要

Using mouse model for graft versus host disease (GVHD), we studied effects of mesenchymal stem cell (MSC) on severity, prognosis of GVHD. 2×107 bone marrow cells isolated form C57BL/6 mice were transplanted to lethally irradiated BALB/c mice. An apparent GVHD was observed 7 days after marrow transplantation (BMT), which continued to day 28, the last day for observations. To develop various severity in GVHD, we added various number of spleen cells obtained from C57BL/6 mice. 1×10 spleen cells plus 1×107 marrow cells developed lethal GVHD. More than 50% of recipients dyed before day14. Using this very severe GVHD model, we exploited whether transplantation of MSC decrease GVHD severity in this particular model. MSC were prepared using Mruine Mesencult culture system. Cell surface markers of our MSC were CD45^-, CD11b-, Sca+, CD44+. These MSC could differentiate to osteoblasts and lipocytes under appropriate conditions. Using various number of MSC, GVHD model was challenged for effects of MSC transplantation. MSCs were transplanted on either the day of BMT or one day after BMT. These mice were compared to those of non MSC recipient mice which were received only bone marrow cells. Clinical symptom, body weight, survival date and pathological findings were studied at day7, 14,21 and 28 after BMT, though none of these findings were changed in both MSC recipients and BMT only recipients. We are planning to do BMT with immunosuppressive reagent plus MSC on different severity of GVHD model as a next trial

使用移植物抗宿主病 (GVHD) 小鼠模型，我们研究了间充质干细胞 (MSC) 对 GVHD 严重程度和预后的影响，将从 C57BL/6 小鼠中分离的 2×107 骨髓细胞移植到致死照射的 BALB/c 小鼠中。骨髓移植 (BMT) 后 7 天观察到明显的 GVHD，并持续到第 28 天，即观察的最后一天。添加了从 C57BL/6 小鼠获得的不同数量的脾细胞和 1×107 骨髓细胞，超过 50% 的受体在第 14 天之前染色。 MSC 降低了该特定模型中的 GVHD 严重性 MSC 使用 Mruine Mesencult 培养系统制备，我们的 MSC 的细胞表面标记为 CD45^-， CD11b-、Sca+、CD44+。在适当的条件下，使用不同数量的MSC，对MSC移植的效果进行挑战。将这些小鼠与仅接受骨髓细胞的非MSC受体小鼠进行比较，在第7、14、21天研究临床症状、体重、存活日期和病理结果。 BMT 后 28 例，尽管在 MSC 接受者和仅 BMT 接受者中这些结果都没有改变，我们计划在下一个试验中对不同严重程度的 GVHD 模型进行免疫抑制剂加 MSC 的 BMT。