Cyclosporin A Promotes Invasion and Migration of Extravillous Trophoblast Cells Derived from Human-Induced Pluripotent Stem Cells and Human Embryonic Stem Cells

被引:2
作者
Wang, Jiaxing [1 ,2 ,3 ,4 ,5 ]
Long, Ping [1 ,2 ,3 ,4 ]
Tian, Shengnan [1 ,6 ]
Zu, Weihua [1 ,2 ,3 ,4 ]
Liu, Jing [1 ,7 ]
Wu, Bangyong [1 ,2 ,3 ,4 ]
Mao, Jilong [1 ,2 ,3 ,4 ]
Li, Dan [1 ,8 ]
Ma, Yanlin [1 ,2 ,3 ,4 ]
Huang, Yuanhua [1 ,2 ,3 ,4 ]
机构
[1] Hainan Med Univ, Affiliated Hosp 1, Hainan Prov Key Lab Human Reprod Med & Genet Res, Haikou, Peoples R China
[2] Hainan Med Univ, Affiliated Hosp 1, Dept Reprod Med, Haikou, Peoples R China
[3] Hainan Med Univ, Affiliated Hosp 1, Hainan Prov Clin Res Ctr Thalassemia, Haikou, Peoples R China
[4] Hainan Med Univ, Affiliated Hosp 1, Haikou Key Lab Preservat Human Genet Resource, Haikou, Peoples R China
[5] Guangxi Med Univ, Affiliated Hosp 1, Dept Prenatal Diag & Genet Dis, Nanning, Peoples R China
[6] Shandong Univ, Hosp 2, Dept Gynecol, Jinan, Peoples R China
[7] Zhengzhou Univ, Affiliated Hosp 1, Dept Reprod Med, Zhengzhou, Peoples R China
[8] Haikou Women & Children Hosp, Dept Reprod Med, Haikou, Peoples R China
基金
中国国家自然科学基金;
关键词
extravillous trophoblast; Cyclosporin A; human-induced pluripotent stem cells; human embryonic stem cells; invasion; migration; EPITHELIAL-MESENCHYMAL TRANSITION; HUMAN PLACENTATION; IN-VITRO; DIFFERENTIATION; MODELS; PROLIFERATION;
D O I
10.1089/scd.2022.0144
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Extravillous trophoblast (EVT) cells play an essential role in the maternal-fetal interaction. Although abnormal development and function of EVT cells, including impaired migration and invasion capability, are believed to be etiologically linked to severe pregnancy disorders including pre-eclampsia, the associated molecular mechanisms are not clear due to the lack of an appropriate cell model in vitro. Cyclosporin A (CsA) is a macrolide immunosuppressant and also used in clinic to improve pregnancy outcomes. However, whether CsA has any effects on the function of EVT cells has not been well investigated. In this study, we induced differentiation of human-induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) into EVT cells (hiPSC-EVT and hESC-EVT cells, respectively) by Y27632, neuregulin-1 (NRG1), A83-01, and matrigel, and collected these derived EVT cells by flow cytometry for sorting cells positive for double human leukocyte antigen-G (HLA-G) and Cytokeratin7 (KRT7), both of which are EVT markers. We then investigated the effects of CsA on the invasion and migration of these derived EVT cells. We found that the hiPSC-EVT and hESC-EVT cells expressed high levels of the EVT markers such as KRT7, integrin alpha 5 (ITGA5), and HLA-G but low levels of OCT4, a stem cell marker, and that CsA significantly promoted the invasion and migration of hiPSC-EVT and hESC-EVT cells compared with HTR-8/SVneo cells. These results represent a possible cell model for studying the function of EVT cells and mechanism of pregnancy-related disorders associated with EVT. In addition, CsA may be used to treat pregnancy complications in clinic associated with deficient EVT function.
引用
收藏
页码:60 / 74
页数:15
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