1 Department of Biomedical Science, CHA University , Seoul, Republic of Korea.
Stem Cells Dev. 2014 Jan 15;23(2):132-45. doi: 10.1089/scd.2012.0674. Epub 2013 Oct 19.
Tightly regulated trophoblast invasion and immunomodulation at the feto-maternal interface is important during implantation and fetal development. Although trophoblasts as a pregnancy-specific cell has been reported to be a key factor capable of regulating certain events during implantation, however, its regulatory mechanisms are still unclear. In this study, we analyzed the effects of chorionic plate-derived mesenchymal stem cells (CP-MSCs) and human placenta extract (hPE) isolated from human normal placentas on trophoblasts invasion and immune responses. We investigated the effects of CP-MSCs, hPE treatment, and their combination on trophoblasts invasion and on T-cells suppression through human leukocyte antigen-G (HLA-G) expression. Trophoblasts invasion was significantly increased by co-culture of CP-MSCs or by hPE treatment (P<0.05), and enhanced by the combination of CP-MSCs and hPE treatment (P<0.05). The proliferation of T-cells was decreased by co-culture of CP-MSCs and hPE treatment, whereas the population of regulatory T-cells was increased (P<0.05). Also, the dynamics alterations of multiple cytokines were observed in the culture supernatants of trophoblasts and T-cells depending on CP-MSCs co-culture and hPE treatment. Interestingly, the concentration of soluble HLA-G was increased by CP-MSCs co-culture, by hPE treatment and by combination of them on trophoblasts and activated T-cells (P<0.05). These findings suggested that CP-MSCs and hPE can regulate trophoblasts invasion and T-cell by alteration of HLA-G expression. These results will provide understandings of trophoblasts invasion and the immunological network at the feto-maternal interface during pregnancy and contribute to the foundation of a new treatment strategy for pregnancy disorders.
在着床和胎儿发育过程中，胎母体界面上紧密调节的滋养细胞浸润和免疫调节非常重要。尽管滋养细胞作为一种妊娠特异性细胞，已被报道是调节着床过程中某些事件的关键因素，但它的调节机制尚不清楚。在这项研究中，我们分析了源自人正常胎盘的绒毛膜板衍生间充质干细胞（CP-MSCs）和人胎盘提取物（hPE）对滋养细胞浸润和免疫反应的影响。我们研究了 CP-MSCs、hPE 处理及其组合对滋养细胞浸润以及通过人类白细胞抗原-G（HLA-G）表达对 T 细胞抑制的影响。CP-MSCs 共培养或 hPE 处理显著增加了滋养细胞的浸润（P<0.05），CP-MSCs 和 hPE 联合处理增强了这种浸润（P<0.05）。CP-MSCs 和 hPE 共培养降低了 T 细胞的增殖，而调节性 T 细胞的数量增加（P<0.05）。此外，还观察到根据 CP-MSCs 共培养和 hPE 处理，滋养细胞和 T 细胞培养上清液中的多种细胞因子动态发生变化。有趣的是，CP-MSCs 共培养、hPE 处理以及它们的联合处理增加了滋养细胞和激活的 T 细胞可溶性 HLA-G 的浓度（P<0.05）。这些发现表明 CP-MSCs 和 hPE 可以通过改变 HLA-G 表达来调节滋养细胞浸润和 T 细胞。这些结果将为理解妊娠期间滋养细胞浸润和胎母体界面的免疫网络提供依据，并为妊娠疾病的新治疗策略奠定基础。
