Amniotic Fluid Cells Used to Create Organoids for Fetal Disease Research
Researchers have successfully grown organoids, 3D bundles of cells that mimic tissue, from cells taken from the fluid around growing fetuses. These organoids have the potential to provide valuable insights into diseases that develop in the fetus during pregnancy. The study, published in Nature Medicine, marks the first time that organoids have been grown directly from cells taken from ongoing pregnancies.
The researchers collected amniotic fluid from 12 pregnancies between the 16th and 34th weeks of gestation. They grew organoids from lung, kidney, and small intestine cells shed into the amniotic fluid. This breakthrough could pave the way for a better understanding of congenital conditions and personalized treatment for individual fetuses in the future.
In the United Kingdom alone, around 13,000 children were born with at least one congenital anomaly in 2020 out of nearly 600,000 births. The organoids created from amniotic fluid cells could potentially shed light on how these conditions progress and provide valuable information for developing targeted treatments.
Traditionally, organoids are grown from cells taken from biopsies, which are then reprogrammed into induced pluripotent stem cells capable of differentiating into any type of cell. However, this process is time-consuming. The researchers in this study used amniotic fluid as a source of living cells, allowing them to study fetal tissue at later stages of development.
Access to fetal tissue remains limited for researchers, making it challenging to model fetal tissue using organoids. One option is to use tissue from terminated pregnancies, but this is accompanied by ethical issues and is limited to earlier stages of gestation. By using amniotic fluid cells, the researchers can study fetal tissue at later stages of development.
The samples were obtained through standard prenatal care procedures such as amniocentesis or amniotic drainage. The researchers isolated individual cells from the samples and characterized their origins. Most of the cells were from the epithelial layer, which covers an organ’s surfaces. Epithelial cells naturally come together and assemble, making them ideal for forming organoids. These organoids are particularly relevant for studying congenital diseases that involve epithelial tissues.
The team successfully grew organoids from three organs: the small intestines, kidneys, and lungs. The organoids expressed the genes and proteins of the organs they originated from. Additionally, the researchers modeled congenital diaphragmatic hernia (CDH), a disorder where the diaphragm fails to develop correctly, using cells from affected samples.
Unlike organoids made from pluripotent stem cells, the amniotic fluid cells already have an organ identity. This eliminates the need for reprogramming or manipulation of the cells. The relatively simple techniques used in this study also reduced the time needed to grow the organoids to just four to six weeks, compared to the five to nine months typically required when using stem cells.
While the research is not yet ready for clinical application, the organoids grown from amniocentesis could potentially be used to screen treatments. However, more complex congenital disorders that affect multiple tissue layers may require additional research. It may not be possible to use this method to model organs that do not shed cells into the amniotic fluid, such as the brain or heart.
Further studies are needed to compare the capabilities of these organoids with those derived from biopsies or pluripotent stem cells. Researchers will need to assess their responsiveness to drugs and how faithfully they reveal the underpinnings of diseases. The next steps for the researchers involved in this study include testing the capabilities of CDH organoids for modeling the disease and comparing them to patient data.
Overall, this groundbreaking research using amniotic fluid cells to create organoids opens up new possibilities for studying fetal diseases and developing personalized treatments. It represents a significant step forward in understanding and addressing congenital conditions that affect thousands of children worldwide.
