A team of scientists, including University College London, has reported a major breakthrough in stem cell research: cells collected from human amniotic fluid samples can generate organoids containing multiple tissue types without terminating pregnancy. These organoids provide important means of understanding late pregnancy development and also contribute to the treatment and research of congenital malformations. The research is published in the new issue of Nature Medicine. Organ like structures are three-dimensional models created using human stem cells, similar to fetal tissue. The current methods for obtaining organoids for pregnancy modeling (mostly derived from fetal tissue after death) involve legal and ethical issues and are typically only used within 20-22 weeks after conception, which limits research on late pregnancy development. The research team evaluated epithelial cells collected from human amniotic fluid, which were obtained from prenatal examinations of 12 pregnancies (between 16 and 34 weeks of pregnancy). Using single-cell sequencing, the team identified and isolated epithelial cells from the fetal gastrointestinal, renal, and pulmonary tracts. To explore whether these cells can be used to produce organoids, the team cultured these cells and observed that they began to proliferate and self-organize into three-dimensional organoids, which were visible within two weeks. They found that these cells form tissue-specific native fetal organs, namely the small intestine, kidneys, and lungs, and exhibit functional characteristics of the source tissue. Using this technology, the team cultivated lung like organs that reproduced certain features of congenital diaphragmatic hernia from amniotic fluid and tracheal fluid cells of fetuses. Researchers believe that the new findings demonstrate an alternative method for cultivating fetal organoids that does not require termination of pregnancy, helps address long-standing ethical concerns, and can be used to study the late stages of pregnancy. This method may provide an opportunity for the development of advanced prenatal models and personalized therapies by autologous derived fetal primary organoids during pregnancy. They pointed out that further research is needed to verify the translational impact of these findings. (Lai Xin She)