New method creates human trophoblast stem cells from late-gestation placentas

Researchers at Kumamoto University, Tohoku University, and Kyushu University have developed a robust method for producing human trophoblast stem cells (hTSCs) from late-gestation placentas, opening a new avenue for studying pregnancy complications using patient-derived cells.

The placenta plays a vital role during pregnancy, supplying the developing fetus with oxygen and nutrients. Its major cell type, the trophoblast, helps establish and maintain the placenta. When trophoblast function is disrupted, it may contribute to pregnancy complications such as fetal growth restriction, preterm birth, and preeclampsia. However, researchers have lacked suitable human experimental models for investigating how these disorders develop.

Human trophoblast stem cells are a powerful research tool because they can proliferate and differentiate into different types of trophoblast cells. Although the research team previously established methods for deriving hTSCs from early-stage placentas, obtaining these cells efficiently from late-gestation placentas has remained challenging.

The team discovered that trophoblast cells from late-gestation placentas display characteristics of cellular aging. By temporarily introducing factors that suppress cellular aging and promote stem-cell properties, together with short-term suppression of genes that restrict cell proliferation, the researchers were able to efficiently generate hTSCs while avoiding detectable chromosomal abnormalities. The resulting cells showed proliferation and differentiation capabilities comparable to hTSCs derived from early-stage placentas.

The researchers then applied the method to placental samples from 10 patients with preeclampsia. The patient-derived hTSCs reproduced key features associated with the disease: trophoblast cells showed reduced invasive activity, while differentiated cells produced lower levels of placental growth factor (PGF), an important factor involved in blood-vessel formation.

“These findings provide a technological foundation for establishing disease-specific trophoblast stem cell models,” said Hiroaki Okae, Professor at Kumamoto University’s Institute of Molecular Embryology and Genetics (IMEG).

The researchers expect these patient-derived models to help uncover the molecular mechanisms underlying preeclampsia and other pregnancy complications, and ultimately support the development of new therapeutic strategies. The study was published in Proceedings of the National Academy of Sciences (PNAS) on June 11, 2026.