Cells Shed by Fetuses Have Been Grown Into Mini-Organs

How can we ethically study the final stages of pregnancy? That sounds like an obvious question, but it has puzzled researchers for decades.

For obvious reasons, whole human embryos cannot be grown and observed in a laboratory setting, so a lot of our understanding of embryo development comes from the study of animals. In recent years, scientists have developed a new method for studying embryos using human tissues. This method centers around the concept of three-dimensional mini-organs called organoids.

These organoids are grown from human stem cells and can be programmed to resemble fetal-like tissues. The mini-organs allow researchers to study the development of human embryos at a tissue level, providing insights into various developmental disorders and their potential treatments.

However, to date these stem cells have mostly been obtained from terminated pregnancies, which brings an array of legal and ethical complications. It also means that these cells can be accessed only up until roughly 22 weeks after conception, limiting research into what happens during the later stages of pregnancy. But this may all be about to change.

In a new study, published in the journal Nature Medicine, researchers from University College London demonstrated that these cells can be collected from the fluid that surrounds the baby during pregnancy—known as amniotic fluid.

Because it is in contact with the growing fetus, the amniotic fluid contains measurable levels of fetal cells, which can then be extracted and cultured in a lab to create mini-model organs without touching the fetus itself. This would allow researchers to access and analyze fetal stem cells in a noninvasive way during the later stages of pregnancy.

Within just two weeks, the researchers began to see the proliferation and self-organization of these extracted cells into model organoids. In particular, these organoids grew to resemble tissue from the small intestine, kidney and lungs, even displaying functional features of their origin tissues.

"This work represents a surprising advancement in stem cell technology to grow organoids from cells obtained from amniotic fluid," Shota Nakanoh, a postdoctoral researcher in the epigenetics research program at the Babraham Institute who was not involved in the research, said in a statement.

"The authors covered 12 pregnancies, 42 amniotic fluid samples and 423 amniotic fluid organoid lines," she said. "They used the latest sequencing technologies [and] also confirmed the features important for the functions of original organs.

Nakanoh continued: "The pipeline of amniotic fluid organoid formation described here would bring a great advantage in the field since it is non-invasive and can utilise samples obtained by routine and current methods. It offers a variety of applications including research on foetal organs, disease modelling during development, pre-natal diagnostic tests for babies and so on. Also, sampling of healthy mothers and babies will provide insight into the biology of development and pregnancy."

Nakanoh said that some cell types might be harder to grow into model organoids than others, but the study's results were nevertheless exciting.

Roger Sturmey, a professor of reproductive medicine at the U.K.'s University of Hull, said in a statement that the method for extracting this amniotic fluid during pregnancy "is an established method called amniocentesis, which doctors can use to examine the presence of certain conditions during pregnancy."

Sturmey added that these mini-organ models were not representative of complete human organs but rather models of specific tissues.

"Organoids typically contain only a selection of the cell types found in a full organ, and in this research, organoids formed from the epithelial cells, which are the cells that line many organs," he said. "The team were able to generate organoids that model lung, kidney, and intestinal tissue from fetal cells in the amniotic fluid."

The new research paves the way for scientists to study how key organs are formed and perform their function in the developing fetus without having to extract tissue directly from a fetus, Sturmey said. This is typically available only from tissue that is donated to research following the termination of a pregnancy.

The research may also reveal "early origins of adult disease by highlighting what happens when the cells of key tissues within fetuses malfunction," he said.