Department of Hematology, Xinqiao Hospital, Chongqing, China.
Cytotherapy. 2011 Jan;13(1):83-91. doi: 10.3109/14653249.2010.501786. Epub 2010 Jul 22.
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.
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.
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.
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.
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。
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。
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。
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。