Organoids made from uterus fluid may help treat fetuses before birth

Babies born with serious medical conditions could one day get better diagnoses and treatments while in the uterus, thanks to a new technique that involves taking samples of cells from fluid in the uterus and growing them in a dish.

In a world first, Paolo De Coppi at Great Ormond Street Hospital in London and his colleagues have shown that fetal cells from amniotic fluid can be coaxed into forming miniature balls of lung, kidney or small intestinal tissue. They also showed these lung organoids could potentially help guide the treatment of babies born with a sometimes-fatal lung condition called congenital diaphragmatic hernia (CDH).

The technique hasn’t yet been used to treat any children, but the results show that is possible in principle, says De Coppi. It could also be modified to help in various other congenital conditions in a strategy the researchers call “personalised prenatal medicine”.

The idea exploits a recent approach in which cells in a dish are coaxed to grow into tissue organoids, about the size of a lentil, which take up a three-dimensional structure. These then capture certain aspects of the tissue in question, including whether it is healthy or growing abnormally, better than the standard technique of growing cells in a two-dimensional layer.

The team has now shown that samples of amniotic fluid taken during pregnancy contain fetal cells capable of forming organoids of tissue from the lungs, kidneys and small intestine.

Studying organoids made from cells from a fetus known to have a congenital condition may be able to give doctors more information about exactly what form it will take, how severe it is and how it could be treated.

In the study, the team created organoids for 12 fetuses with CDH, where the abdominal organs push up into the chest and stop the left lung from growing properly. The condition can be treated while the fetus is in the uterus by pushing a balloon into the lung to expand it, helping it to develop better.

The researchers created lung organoids from the fetuses both before and after the balloon treatment. They saw hints that the organoids created after the treatment were behaving more like healthy lung tissue than the ones made beforehand, suggesting that the treatment was successful.

The organoid technique could therefore be used to monitor if the treatment has worked, as well as gauging if it is needed in the first place, as doctors only carry out this intervention in the severest forms of the condition.

“This has a lot of potential for functional diagnoses,” says De Coppi. “We know how to make diagnoses based on imaging, but sometimes there’s a large spectrum of [condition severity] possible. We hope to offer a better prenatal diagnostic tool.”

“If you have the possibility to categorise a disease into mild, moderate or severe, that’s a great achievement,” says Cecilia Götherström at the Karolinska Institute in Stockholm, Sweden.

Holm Schneider at University Hospital Erlangen in Germany says the approach also suggests the possibility of one day turning organoids into mature tissues for implanting into babies after birth, for instance in conditions where part of the intestine is missing. “If you could engineer gut-like structures to be available after birth for these children, you would be in a much better position,” he says.