Ko Gun, Jeon Tae-Joon, Kim Sun Min
Department of Biological Sciences and Bioengineering, Inha University, 100 Inha-ro, Michuhol-gu, Incheon 22212, Republic of Korea.
Department of Biological Engineering, Inha University, 100 Inha-ro, Michuhol-gu, Incheon 22212, Republic of Korea.
Micromachines (Basel). 2022 Dec 14;13(12):2216. doi: 10.3390/mi13122216.
In the placenta, substances such as nutrients, oxygen, and by-products are exchanged between the mother and the fetus, and the proper formation of the placenta determines the success of pregnancy, including the growth of the fetus. Preeclampsia is an obstetric disease in which the incomplete formation of the placenta occurs, which is known to occur when there is an abnormality in the invasion of trophoblast cells. The invasion of trophoblast cells is controlled by oxygen concentration, and HIF-1α changes according to oxygen concentration, showing a difference in cell mobility. MMP-2 and MMP-9 are observed to be high in the endometrium involved in trophoblast invasion, and the expression is regulated according to the oxygen concentration. In this experiment, cell culture was conducted using a gel-patterned system with a hypoxic chamber. Before the chip experiment, the difference in the expression of MMP-2 and MMP-9 according to the oxygen concentration was confirmed using a hypoxia chamber. After that, trophoblast cells (HTR8/SVneo) and endothelial cells (HUVECs) were separated and cultured through a physical barrier through a hydrogel on a microfluidic chip. Cells were cultured in a hypoxic chamber under controlled oxygen levels. It was confirmed that the mobility of trophoblast cells in culture on the chip was upregulated in a hypoxic environment through oxygen control. This suggests that the formation of a hypoxic environment in the endometrium where the invasion of trophoblast cells occurs plays a role in increasing cell mobility.
在胎盘中,营养物质、氧气和代谢产物等物质在母体和胎儿之间进行交换,胎盘的正常形成决定了妊娠的成功,包括胎儿的生长。子痫前期是一种产科疾病,其胎盘形成不完全,已知当滋养层细胞侵袭异常时会发生。滋养层细胞的侵袭受氧浓度控制,HIF-1α会根据氧浓度发生变化,表现出细胞迁移率的差异。在参与滋养层侵袭的子宫内膜中观察到MMP-2和MMP-9水平较高,且其表达根据氧浓度进行调节。在本实验中,使用带有缺氧箱的凝胶图案系统进行细胞培养。在芯片实验之前,使用缺氧箱确认了MMP-2和MMP-9表达随氧浓度的差异。之后,通过微流控芯片上的水凝胶物理屏障分离并培养滋养层细胞(HTR8/SVneo)和内皮细胞(HUVECs)。细胞在可控氧水平的缺氧箱中培养。通过氧控制证实,芯片上培养的滋养层细胞在缺氧环境中的迁移率上调。这表明在滋养层细胞发生侵袭的子宫内膜中形成缺氧环境在增加细胞迁移率方面发挥作用。