Researchers created 3D models of developing organs from fetal cells, which are present in amniotic fluid, to help prenatal diagnosis and speed up innovative therapeutic strategies in rare diseases.
Congenital disorders, according to WHO (World Health Organization), affect 6% of newborns globally, causing significant illness and death and therefore representing a major health burden, especially in low- and middle-income countries with limited treatment options. These prenatal anomalies, also known as birth defects, develop prenatally during intra-uterine life and may be identified at birth, or later on.
Precision medicine in fetal diagnosis and therapy is a hot topic. Current prenatal diagnosis heavily relies on imaging techniques and analysis of fetal DNA from mother’s blood. However, these methods have limitations in predicting disease severity and testing treatment options. In addition, available personalized models of fetal diseases rely on ethically complicated and legally restricted fetal tissue samples (e.g., stem cells), obtainable only up to mid-pregnancy or at pregnancy termination. These limitations hamper the study of late time points of fetal development and therefore hinder research and prenatal medicine.
A new approach proposes isolating and expanding fetal epithelial cells from amniotic fluid (AF) during pregnancy. AF samples can be collected throughout the entire gestation during standard prenatal procedures, thus offering a convenient opportunity to obtain samples without additional burden on patients. Leveraging advanced cellular and molecular biology techniques, researchers were able to generate organoids (i.e. miniaturized version of human organs grown in vitro) of small intestines, kidneys and lungs starting from these AF-derived cells. These “mini-organs” exhibited molecular and functional features of the fetal tissues they originated from and will offer a new tool to study the functionality of developing organs during all the stages of prenatal life. As proof-of-concept of their discovery, they generated organoids from AF-derived cells isolated from fetuses affected by congenital diaphragmatic hernia (CDH). CDH is a rare birth defect affecting 1 in 3,000 newborns, with high mortality rate, which involves a malformed diaphragm leading to underdeveloped lungs. Notably, lung organoids derived from CDH cells have shown some disease-specific traits and thus will offer the unique opportunity to test tailored therapeutic strategies.
This research is not ready to be transferred to the clinic yet. Further studies will be needed to understand how faithfully AF-derived organoids model congenital diseases and whether more complex birth defects affecting multiple tissues can be studied with this technique. However, this innovative approach offers a minimally invasive way to create patient-specific organoids and potentially paves the way to in vitro personalized prenatal disease modeling and development of new therapies.
By Roberto Oleari, Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, University of Milan
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