Generation of Bona Fide Human Induced Trophoblast Stem Cells from Term Umbilical Cord

Placentation disorders such as severe fetal growth restriction and preeclampsia have their origin in the first trimester of pregnancy, whereas symptoms typically present later on. To be able to study the pathogenesis of these diseases, there is a need for a reliable model system of early placenta development with known pregnancy outcomes. Therefore, we aimed to optimize the generation of human induced trophoblast stem cells (iTSCs) from term umbilical cord using a direct reprogramming approach. In this, we added three supplements—A-485 (CREBBP/EP300 inhibitor), BMP4 or EPZ-6438 (PRC2 inhibitor)—that could potentially boost iTSC induction. The generated iTSCs fulfilled the criteria for bona fide first-trimester trophoblasts and exhibited transcriptional similarity to TSCs derived from first-trimester placental tissue, while the supplements tested did not substantially enhance iTSC induction.