New full-term placental stem cells could transform research on late-pregnancy complications

Pregnancy complications such as preeclampsia and preterm birth often arise during the late stage of pregnancy. However, researchers have primarily relied on placental cells from early pregnancy to study these conditions, which may not fully reflect the biology of late-stage complications. Now, a research team in Japan has successfully developed human placental stem cells from the smooth chorion (a part of the placenta) taken from full-term pregnancies. These new stem cells, called Ch-TS cells, share the same characteristics as placental stem cells from early pregnancy and can develop into the key cell types essential for proper placental function. This advancement allows scientists to study placental complications using cells from the actual time period when these complications occur, potentially leading to better understanding, earlier detection, and improved treatments for pregnancy-related conditions.

The research was led by Professor Masatsugu Ema and Assistant Professor Masanaga Muto from the Department of Stem Cells and Human Disease Models at the Research Center for Animal Life Science, Shiga University of Medical Science (Professor Masatsugu Ema is also a Principal Investigator at WPI-ASHBi). The findings were published in the journal Placenta on July 31, 2025.

Background

The placenta serves as a lifeline between mother and baby. Through the umbilical cord, it delivers oxygen and nutrients to the developing baby while removing waste from the baby's blood. Specialized placental cells called trophoblasts transport nutrients from the mother and remodel maternal blood vessels to support the growing baby. When these cells malfunction, serious pregnancy complications can develop, including preeclampsia (dangerously high blood pressure during pregnancy), fetal growth restriction, and placental abruption (early separation of the placenta from the uterus). These placenta-mediated pregnancy complications are often detected during the late stage of pregnancy, affecting thousands of families worldwide every year.

Scientists have been working to understand how pregnancy complications develop, but studying the human placenta during pregnancy presents significant technical challenges and ethical concerns. To address this obstacle, researchers have developed laboratory models using stem cells derived from placental tissue that can grow and develop under controlled conditions outside the body. Until now, these valuable research tools, called trophoblast stem cells, have primarily been created from placentas obtained during early pregnancy. Since most complications occur during the late stage of pregnancy, scientists need a more relevant model to study these conditions and improve treatment and prevention strategies.

Key Findings

Researchers have long believed that the source of trophoblast stem cells in the placenta might have disappeared during late pregnancy, since deriving these cells from full-term placentas has proven difficult. This study overturns this assumption: scientists successfully isolated trophoblast cells from the smooth chorion, the outermost fetal membrane of full-term placentas, and established stable trophoblast stem cell lines called Ch-TS cells. These laboratory-cultured cells displayed all the key characteristics of human trophoblast cells and could differentiate into the two main cell types essential for healthy placental function: extravillous trophoblasts, which invade and remodel the mother's uterine tissue, and syncytiotrophoblasts, which facilitate nutrient and oxygen exchange between mother and baby. These findings demonstrate that term smooth chorion trophoblast cells still retain stem cell potential, indicating a striking difference between trophoblasts in the term placenta and those in the term smooth chorion.

Gene expression analysis confirmed that the characteristics of Ch-TS cells are similar to those of the originally reported trophoblast stem cells, validating their potential as a research tool. At the same time, Ch-TS cells exhibited distinct gene expression patterns compared to other stem cells derived from term placentas using alternative culture methods. Importantly, Ch-TS cells more resemble the originally reported trophoblast stem cells than other term-derived stem cells, highlighting their potential to model human placental development.

Future Perspectives

Studying trophoblast stem cells from term placentas offers a powerful platform for investigating the underlying mechanisms behind pregnancy complications such as preeclampsia and preterm birth. Because the smooth chorion helps maintain the integrity of fetal membranes, Ch-TS cells could also be used to study complications like premature rupture of membranes.

Using cells from full-term placentas avoids the ethical concerns associated with early pregnancy tissue, making research more accessible and easier to conduct. The ability to grow trophoblast stem cells from the smooth chorion also enables scientists to create laboratory models of the placenta and fetal membranes, helping researchers better understand pregnancy complications and develop strategies to prevent or treat them. Overall, this advancement opens new doors for pregnancy research and may ultimately lead to improved outcomes for mothers and babies affected by late-pregnancy complications.

KYOTO, Japan – August 20, 2025

Glossary

• Trophoblast: Specialized placental cells that are crucial in supplying nutrients to the fetus and for maintaining pregnancy.
• Smooth chorion: the outer layer of the fetal membranes that surrounds the baby during pregnancy like a protective wrapper. It's called "smooth" because it doesn't have the finger-like projections (villi) found in other parts of the placenta, and it helps maintain the integrity of fetal membranes.