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人脐带血源基质细胞预防亲缘半相合干细胞移植后小鼠移植物抗宿主病。

Human umbilical cord blood-derived stromal cells prevent graft-versus-host disease in mice following haplo-identical stem cell transplantation.

机构信息

Department of Hematology, Xinqiao Hospital, Chongqing, China.

出版信息

Cytotherapy. 2011 Jan;13(1):83-91. doi: 10.3109/14653249.2010.501786. Epub 2010 Jul 22.

Abstract

BACKGROUND AIMS

Human umbilical cord blood-derived stromal cells (hUCBDSC) comprise a novel population of CD34(+) cells that has been isolated in our laboratory. They have been shown previously not only to be non-immunogenic but also to exert immunosuppressive effects on xenogenic T cells in vitro. This study investigated the role of hUCBDSC in immunomodulation in an acute graft-versus-host disease (GvHD) mouse model after haplo-identical stem cell transplantation.

METHODS

Acute GvHD was induced in recipient (B6 × BALB/c)F(1) mice by irradiation (750 cGy) followed by infusion of bone marrow cells and splenocytes from donor C57BL/6 mice. hUCBDSC were co-transplanted in the experimental group. The survival time, body weight and clinical and histopathologic scores were recorded after transplantation. The expression of surface markers [major histocompatibility complex (MHC) I, MHC II, CD80 and CD86] on CD11c(+) dendritic cells (DC), and the percentage of CD4(+) regulatory T cells (Treg), in the spleens of recipient mice were examined by flow cytometry.

RESULTS

The survival time was significantly prolonged, and the clinical and histopathologic scores were reduced in mice co-transplanted with hUCBDSC. The expression levels of the surface markers on DC were significantly lower in mice transplanted with hUCBDSC compared with those without. The proportion of CD4(+) Treg in the spleen was also increased in mice transplanted with hUCBDSC.

CONCLUSIONS

These results from a GvHD mouse model are in agreement with previous in vitro findings, suggesting that hUCBDSC possess immunosuppressive properties and may act via influencing DC and CD4(+) Treg.

摘要

背景目的

人类脐带血源基质细胞(hUCBDSC)包含一个新型的 CD34+细胞群,该细胞群已在我们实验室中分离出来。先前的研究表明,它们不仅具有非免疫原性,而且还能在体外对异种 T 细胞发挥免疫抑制作用。本研究旨在探讨 hUCBDSC 在同种异体造血干细胞移植后急性移植物抗宿主病(GvHD)小鼠模型中的免疫调节作用。

方法

通过照射(750cGy)和输注来自供体 C57BL/6 小鼠的骨髓细胞和脾细胞,在受体(B6×BALB/c)F1 小鼠中诱导急性 GvHD。在实验组中共同移植 hUCBDSC。移植后记录生存时间、体重以及临床和组织病理学评分。通过流式细胞术检测受体小鼠脾脏中 CD11c+树突状细胞(DC)表面标志物[主要组织相容性复合体(MHC)I、MHC II、CD80 和 CD86]的表达以及 CD4+调节性 T 细胞(Treg)的百分比。

结果

与未移植 hUCBDSC 的小鼠相比,共移植 hUCBDSC 的小鼠的生存时间明显延长,临床和组织病理学评分降低。与未移植 hUCBDSC 的小鼠相比,移植 hUCBDSC 的小鼠 DC 表面标志物的表达水平显著降低。移植 hUCBDSC 的小鼠脾脏中 CD4+Treg 的比例也增加。

结论

这些来自 GvHD 小鼠模型的结果与先前的体外研究结果一致,表明 hUCBDSC 具有免疫抑制特性,可能通过影响 DC 和 CD4+Treg 发挥作用。

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