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同种异体骨髓移植后多能间充质基质细胞对大鼠移植物抗宿主病的免疫抑制作用。

Immunosuppressive effects of multipotent mesenchymal stromal cells on graft-versus-host disease in rats following allogeneic bone marrow transplantation.

机构信息

Gülhane Medical Academy, Department of Hematology, Ankara, Turkey.

Gülhane Medical Academy, Department of Immunology, Ankara, Turkey.

出版信息

Turk J Haematol. 2013 Sep;30(3):256-62. doi: 10.4274/Tjh.2013.0032. Epub 2013 Sep 5.

DOI:10.4274/Tjh.2013.0032
PMID:24385804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3878544/
Abstract

OBJECTIVE

Graft-versus-host disease (GVHD) is a major obstacle to successful allogeneic bone marrow transplantation (allo-BMT). While multipotent mesenchymal stromal cells (MSCs) demonstrate alloresponse in vitro and in vivo, they also have clinical applications toward prevention or treatment of GVHD. The aim of this study was to investigate the ability of MSCs to prevent or treat GVHD in a rat BMT model.

MATERIALS AND METHODS

The GVHD model was established by transplantation of Sprague Dawley rats' bone marrow and spleen cells into lethally irradiated (950 cGy) SDxWistar rat recipients. A total of 49 rats were randomly assigned to 4 study and 3 control groups administered different GVHD prophylactic regimens including MSCs. After transplantation, clinical GVHD scores and survival status were monitored.

RESULTS

All irradiated and untreated control mice with GVHD died. MSCs inhibited lethal GVHD as efficiently as the standard GVHD prophylactic regimen. The gross and histopathological findings of GVHD and the ratio of CD4/CD8 expression decreased. The subgroup given MSCs displayed higher in vivo proportions of CD25+ T cells and plasma interleukin-2 levels as compared to conventional GVHD treatment after allo-BMT.

CONCLUSION

Our results suggest that clinical use of MSCs in both prophylaxis against and treatment of established GVHD is effective. This study supports the use of MSCs in the prophylaxis and treatment of GVHD after allo-BMT; however, large scale studies are needed.

CONFLICT OF INTEREST

None declared.

摘要

目的

移植物抗宿主病（GVHD）是异体骨髓移植（allo-BMT）成功的主要障碍。虽然多能间充质基质细胞（MSCs）在体外和体内表现出同种反应，但它们也具有预防或治疗 GVHD 的临床应用。本研究旨在探讨 MSCs 在大鼠 BMT 模型中预防或治疗 GVHD 的能力。

材料和方法

通过将 Sprague Dawley 大鼠的骨髓和脾细胞移植到致死性照射（950 cGy）的 SDxWistar 大鼠受者中，建立 GVHD 模型。共有 49 只大鼠被随机分配到 4 个研究组和 3 个对照组，接受不同的 GVHD 预防方案，包括 MSCs。移植后，监测临床 GVHD 评分和生存状况。

结果

所有照射未治疗的 GVHD 对照小鼠均死亡。MSCs 与标准 GVHD 预防方案一样有效地抑制致命性 GVHD。GVHD 的大体和组织病理学发现以及 CD4/CD8 表达的比例降低。与 allo-BMT 后常规 GVHD 治疗相比，亚组给予 MSCs 后体内 CD25+T 细胞比例和血浆白细胞介素-2 水平更高。

结论

我们的结果表明，MSCs 在预防和治疗已建立的 GVHD 中的临床应用是有效的。本研究支持 MSCs 在 allo-BMT 后预防和治疗 GVHD 的应用；然而，需要进行大规模研究。

利益冲突

无。

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