Jones B J, Brooke G, Atkinson K, McTaggart S J
Biotherapy Program, Mater Medical Research Institute, South Brisbane, QLD 4101, Australia.
Placenta. 2007 Nov-Dec;28(11-12):1174-81. doi: 10.1016/j.placenta.2007.07.001. Epub 2007 Aug 22.
BACKGROUND/OBJECTIVES: Mesenchymal stem cells (MSC) can be isolated from human placenta and have the potential to contribute to the immunosuppressive properties of placental tissue. The objectives of this study were to investigate the phenotype and differentiation characteristics of MSC derived from human placenta and evaluate the role of the tryptophan degrading enzyme, indoleamine 2,3 dioxygenase (IDO), in mediating their immunosuppressive affect.
MSC obtained from placental tissue (pMSC) were characterised using flow cytometry and tested for multipotency by determining differentiation into all mesenchymal lineages. The immunosuppressive properties of pMSC were tested in allogeneic mixed lymphocyte reactions and IDO expression and activity were measured by semi-quantitative real-time PCR and HPLC respectively.
Multipotent stem cells were isolated from placenta and displayed chondrogenic, osteogenic and limited adipogenic differentiation. Cell surface antigen expression of pMSC was similar to bone marrow MSC (bMSC) with lack of the haematopoietic and common leukocyte markers (CD34, CD45), and expression of adhesion (CD29, CD166, CD44) and stem cell (CD 90, CD105, CD73) markers. Placental MSC were suppressive of allogeneic T-cell proliferation, an effect which was intensified following IDO induction by IFN-gamma. Replenishment of tryptophan or treatment with the IDO-blocker, 1-methyl-tryptophan (1-MT), attenuated the immunosuppressive action of pMSC.
These results suggest that placental tissue contains MSC, which are phenotypically and functionally similar to bMSC, and that IDO is a key mediator of their immunosuppressive effect. Further investigation is needed to determine if pMSC function effects pregnancy outcome.
背景/目的:间充质干细胞(MSC)可从人胎盘中分离得到,且有可能促成胎盘组织的免疫抑制特性。本研究的目的是调查源自人胎盘的MSC的表型和分化特征,并评估色氨酸降解酶吲哚胺2,3-双加氧酶(IDO)在介导其免疫抑制作用中的作用。
使用流式细胞术对从胎盘组织获得的MSC(pMSC)进行表征,并通过确定其向所有间充质谱系的分化来测试其多能性。在异体混合淋巴细胞反应中测试pMSC的免疫抑制特性,并分别通过半定量实时PCR和高效液相色谱法测量IDO的表达和活性。
从胎盘中分离出多能干细胞,其表现出软骨生成、成骨和成脂分化有限。pMSC的细胞表面抗原表达与骨髓MSC(bMSC)相似,缺乏造血和常见白细胞标志物(CD34、CD45),并表达黏附(CD29、CD166、CD44)和干细胞(CD90、CD105、CD73)标志物。胎盘MSC抑制异体T细胞增殖,在IFN-γ诱导IDO后这种作用增强。补充色氨酸或用IDO阻断剂1-甲基色氨酸(1-MT)处理可减弱pMSC的免疫抑制作用。
这些结果表明胎盘组织含有MSC,其在表型和功能上与bMSC相似,且IDO是其免疫抑制作用的关键介质。需要进一步研究以确定pMSC的功能是否影响妊娠结局。