Generation of a Labyrinthine‐Committed, Placental Progenitor Cell Line

Abstract

The The placenta is a multifunctional organ that forms during pregnancy and acts as the interface to exchange nutrients, gases, and wastes between maternal and fetal environments. It also provides protection for the fetus from the maternal immune system. Placental defects such as pre-eclampsia and intrauterine growth restriction (IUGR) are two complications that can occur during pregnancy. Pre-eclamptic mothers develop high blood pressure and proteinuria around their 20th week of pregnancy. In IUGR, babies are under the 10th percentile of birth weight. These complications are due to lack of trophoblast invasion of the maternal arteries and reduced branching of the labyrinth layer of the placenta. The placenta consists of three lineages: giant cells, spongiotrophoblasts, and labyrinthine trophoblasts. The labyrinth layer includes three layers: sinusoidal trophoblast giant cells and two layers of syncytiotrophoblast. Using cell line models to study placental development can lead to new understandings of placental defects. We developed an immortal cell line that can be used to study syncytiotrophoblast differentiation. The mouse cell line, SM10, contains primary cells that have a limited life span of 35 passages in cell culture. To determine if lentivirus was capable of enhancing gene transfer in trophoblast progenitor cells, we constructed a lentivirus with a green fluorescent protein (GFP) gene and infected SM10 progenitor cells before and after differentiation using transforming growth factor- beta (TGF-beta). Surprisingly, SM10 progenitor cells were significantly easier to infect than differentiated cells. Additionally, these infected progenitor cells became immortalized. The new immortal cell line, SM10-GFP, and the primary the SM10 cell line displayed nearly identical functional, morphological, and biochemical responses. Lineage markers further indicated that the SM10-GFP cell line is specifically committed to becoming cells of the syncytiotrophoblast lineage upon differentiation.