Immunofluorescent staining of amniotic fluid organoids in the early stages. Credit: Nat Med 2024.
Scientists have isolated cells from the amniotic fluid of pregnant women and used them to create tri-dimensional cell cultures, called organoids, that resemble the organs of the developing fetus1. Published in Nature Medicine, the study involved a large international collaboration that includes researchers from Politecnico di Milano, the Telethon Institute of Genetics Medicine in Naples, Ospedale Bambino Gesù in Rome and the University of Naples.
“Prenatal studies are now mainly based on imaging or genetic analysis, but do not provide much information on the functionality of organs [of the fetus]” says corresponding author Paolo De Coppi, a paediatric surgeon at Ospedale Bambino Gesù in Rome, and University College London. “Our study opens avenues for investigating foetal development and congenital diseases.”
Organoids are usually derived from biopsy or discarded tissues, something that has been done for many adult tissues. But due to ethical and legal restrictions, isolated tissue-specific foetal stem cells can only be obtained from terminated pregnancies, making it difficult to diagnose prenatal diseases.
The scientists wanted to examine amniotic fluid, which supports and protects the fetus during development and is routinely collected during amniocenteses and other exams. Previous studies had showed that it contains mesenchymal stem cells that subsequently differentiate into various tissues, and hematopoietic ones, giving rise to blood cells2. “But the amniotic fluid also contains secretions, debris and cells from various foetal tissues such as the gastrointestinal tract, kidney and lung,” says co-author, Mattia Gerli from University College London. “We created a map of the epithelial cells content in the fluid, used them to develop organoids, and we found that they had different morphologies”. Using single cells RNA-sequencing and protein analysis, the researchers proved that the 3D cell aggregates resembled features of the organs of origin: small intestine, kidney, and lung.
As a proof-of-concept that these organoids can be used to model an actual disease, the scientists collected epithelial cells from fetuses with Congenital Diaphragmatic Hernia (CDH), a rare congenital malformation where the diaphragm fails to close and the bowel, stomach or liver can move into the chest cavity causing difficulty in breathing. It can be treated by reversibly blocking the trachea of the fetus with a latex balloon. The scientists derived organoids both before and after the implantation of the balloon, and confirmed that the latter functioned better than the former. “We believe that in the future we might monitor diseases with this method,” says Gerli.
