Researchers have grown mini-organs from cells shed by foetuses in the womb in a breakthrough that promises to shed light on human development throughout late pregnancy.
They created the 3D lumps of tissue know as organoids from lung, kidney and intestinal cells recovered from the amniotic fluid that bathes and protects the foetus in the uterus.
It is the first time such organoids have been made from untreated cells in the fluid and paves the way for unprecedented insights into the cause and progression of malformations, which affect 3-6% of babies globally.
Dr Mattia Gerli, a stem cell researcher at UCL, said foetal organoids, which are less than a millimetre wide, would allow scientists to study how foetuses develop in the womb “in both health and disease”, a feat that has so far not been possible.
Because the organoids can be created months before a baby is born, scientists believe they could drive more personalised interventions by helping doctors diagnose any defects and work out how best to treat them.
Organoids are tiny clumps of cells that mimic, to a greater or lesser extent, the features and functions of larger tissues and organs. Scientists use them to study how organs grow and age, how diseases progress, and whether drugs can reverse any damage that arises.
Most organoids are made from adult tissue, but researchers have recently made them from cells obtained from foetuses. The most ethically sensitive were created from tissue collected from terminated foetuses, while others have been made by reprogramming cells into a more embryo-like state.
Writing in Nature Medicine, Gerli and Prof Paolo de Coppi, a foetal surgeon at Great Ormond Street Institute of Child Health, describe how they analysed amniotic fluid taken from 12 pregnant women as part of their routine diagnostic testing. Most of the cells in the amniotic fluid were dead, but a tiny fraction turned out to be stem cells for making the baby’s lungs, kidneys and intestines. The researchers found they could grow these into 3D organoids by injecting them into droplets of gel and culturing them.
To explore how the organoids might be used, the team created lung organoids from the cells of unborn babies with a condition called congenital diaphragmatic hernia, or CDH. Babies with CDH have a hole in the diaphragm, the dome-shaped muscle under the lungs that drives breathing. The hole allows organs in the abdomen to push up on lungs and hamper their growth.
Comparison of organoids from CDH babies before and after treatment showed substantial differences in their development, pointing to a clear benefit from the treatment. “This is the first time that we’ve been able to make a functional assessment of a child’s congenital condition before birth,” said De Coppi.
The same approach could investigate other congenital conditions such as cystic fibrosis, which causes mucus to build up in the lungs, and malformations in the kidneys and gut. Drugs that help alleviate congenital disorders could be tested on the organoids before giving them to the babies, De Coppi said.
Roger Sturmey, professor of reproductive medicine at the University of Hull, said the research paved the way for scientists to study how key organs formed and functioned in unborn babies without tissue donated to research after an abortion. “It may also reveal early origins of adult disease,” he said, “by highlighting what happens when the cells of key tissues within foetuses malfunction”.
