Amniotic Fluid Organoids Can Help Spot Congenital Diseases before Birth

In a groundbreaking study recently published in Nature Medicine, researchers have successfully grown organoids directly from cells extracted from amniotic fluid. This research offers a new avenue for understanding congenital diseases that affect fetal development. 

The team, under the direction of stem-cell biologist Mattia Gerli from University College London, utilized cells obtained from amniotic fluid surrounding growing fetuses. This is a major development in science as it is the first time that organoids are grown directly from cells taken during ongoing pregnancies.  

The main focus of the study was organoids derived from the cells of the small intestine, lung, and kidney cells taken from 12 pregnancies that occurred between the 16th and 34th weeks of gestation. This wide range of developmental stages offers a thorough understanding of organoid formation during various crucial stages of fetal growth. 

The researchers want to learn more about how congenital disorders proceed by using this approach to provide customized treatments for particular fetuses. 

Traditionally, organoids are grown from biopsied cells, which are then transformed into induced pluripotent stem cells. It is a complex and time-consuming process. The innovative method, however, eliminates the need for reprogramming, significantly reducing the time required to grow these 3D cell bundles to just four to six weeks. The simplicity of the technique and its ability to retain the organ identity of the cells make future clinical applications more feasible. 

The samples used in this study were obtained through routine prenatal procedures such as amniocentesis or amniotic drainage, performed during standard prenatal care. By using this non-invasive approach, researchers can obtain amniotic fluid without additional procedures, which ensures ethical considerations are met. 

The researchers isolated individual cells from the amniotic fluid samples. The majority of these cells originated from the epithelial layer. This layer of cells covers organ surfaces and has a natural tendency to come together and assemble, makes it ideal for forming organoids. The study successfully created organoids from three organs such as the small intestines, kidneys, and lungs. By testing the functions of organoids, researchers can examine whether a fetus is healthy or in trouble.  

The researchers acknowledge that further steps are needed before any clinical applications of this research, even though it provides a promising avenue for the study of congenital disorders. It is necessary to address concerns regarding the fidelity of organoids in representing disease characteristics and their responsiveness to drugs. The next step is to evaluate the capabilities of congenital diaphragmatic hernia (CDH) organoids and compare the results with patient data to determine their potential usefulness. 

This study marks a significant step towards understanding and potentially treating congenital diseases as it offers hope for a future where personalized treatments for these conditions may become a reality. 

Reference: 

Gerli, M. F. M. et al. Nature Medicine https://doi.org/10.1038/s41591-024-02807-z (2024).