Patient placentas yield stem-cell models of preeclampsia

A placenta from late pregnancy has usually been a difficult place to start when researchers wanted to grow human trophoblast stem cells. The teams at Kumamoto University, Tohoku University and Kyushu University have now developed a method to do so, creating patient-derived models that reproduced key features of preeclampsia in the laboratory.

The target is the trophoblast, the placenta’s major cell type. It helps establish and maintain the organ, which supplies the developing fetus with oxygen and nutrients. When trophoblast function is disrupted, it may contribute to preeclampsia, fetal growth restriction and preterm birth. Until now, researchers lacked suitable human experimental models for examining how these complications develop.

The team found that trophoblast cells from late-gestation placentas showed signs of cellular aging. It temporarily introduced factors that suppress aging and promote stem-cell properties, while briefly suppressing genes that restrict cell proliferation. The resulting human trophoblast stem cells, or hTSCs, could proliferate and differentiate into different trophoblast types, with capabilities comparable to hTSCs derived from early-stage placentas. The researchers reported no detectable chromosomal abnormalities.

The method was then tested on placental samples from 10 patients with preeclampsia. Their patient-derived cells reproduced two disease-associated signals: trophoblasts had reduced invasive activity, and differentiated cells produced lower levels of placental growth factor, a factor involved in blood-vessel formation.

And then? Researchers now have a laboratory system built from affected patients’ placentas. That could let them probe the molecular mechanisms behind preeclampsia and other pregnancy complications, and support the development of potential therapies. The result is a laboratory research model, not a treatment.