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补充间充质干细胞可提高造血干细胞移植治疗小鼠系统性红斑狼疮的疗效。

Supplementing mesenchymal stem cells improves the therapeutic effect of hematopoietic stem cell transplantation in the treatment of murine systemic lupus erythematosus.

作者信息

Liu R H, Li Y Q, Zhou W J, Shi Y J, Ni L, Liu G X

机构信息

Department of Nephrology, Huizhou Municipal Central Hospital, Huizhou, Guangdong, People's Republic of China.

Department of Genetics, Southern Medical University, Baiyun District, Guangzhou, Guangdong, People's Republic of China.

出版信息

Transplant Proc. 2014 Jun;46(5):1621-7. doi: 10.1016/j.transproceed.2014.03.003.

Abstract

Transplantation of hematopoietic stem cells (HSCs) has been demonstrated to be a promising strategy in the treatment of systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSCs) support hematopoiesis of HSCs and suppress immune response in a dose-dependent manner. Previous study showed that MSCs could alleviate the pathologic conditions of MRL/lpr mice (SLE animal model) when cotransplanted with bone marrow cells. Here, we investigated whether MSCs could improve the therapeutic effect of HSC transplantation in treating MRL/lpr mice in a dose-dependent manner. We found that lethally irradiated MRL/lpr mice were successfully reconstituted with HSCs alone or with various amounts of MSCs. Mice transplanted with HSCs and MSCs in the ratios of 5:1 (HSCs:MSCs) showed less transfusion-associated graft-versus-host reaction, steady body weight, and improved renal functions when compared with mice transplanted with HSCs only and those cotransplanted with MSCs in lower ratios. These results suggest that supplementing MSCs can improve the therapeutic effect of HSC transplantation in treatment of MRL/lpr mice in a dose-dependent manner.

摘要

造血干细胞(HSCs)移植已被证明是治疗系统性红斑狼疮(SLE)的一种有前景的策略。间充质干细胞(MSCs)支持HSCs的造血功能,并以剂量依赖的方式抑制免疫反应。先前的研究表明,MSCs与骨髓细胞共移植时可减轻MRL/lpr小鼠(SLE动物模型)的病理状况。在此,我们研究了MSCs是否能以剂量依赖的方式提高HSC移植治疗MRL/lpr小鼠的疗效。我们发现,经致死剂量照射的MRL/lpr小鼠单独接受HSCs或与不同数量的MSCs共移植后均成功实现造血重建。与仅接受HSCs移植的小鼠以及与较低比例MSCs共移植的小鼠相比,以5:1(HSCs:MSCs)比例移植HSCs和MSCs的小鼠输血相关移植物抗宿主反应更少、体重稳定且肾功能改善。这些结果表明,补充MSCs可以以剂量依赖的方式提高HSC移植治疗MRL/lpr小鼠的疗效。

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