Balls of cells growing from amniotic fluid.Red indicates lung stem cells
Giuseppe Carla, Paolo Di Coppi, Mattia Gurli
Babies born with serious illnesses could one day be better diagnosed and treated in utero, thanks to a new technology that extracts cell samples from intrauterine fluid and grows them in petri dishes.
It can be called the first in the world, Paul Decoby Researchers at Great Ormond Street Hospital in London and colleagues have shown that fetal cells in amniotic fluid can be induced to form microspheres of lung, kidney or small intestine tissue. They also suggest that these lung organoids may help guide treatment for babies born with a sometimes fatal lung disease called congenital diaphragmatic hernia (CDH).
The technique has not yet been used to treat any children, but the results show it is possible in principle, Decoppi said. It could also be modified to help treat a variety of other congenital conditions, something the researchers call “personalized prenatal medicine.”
The idea takes advantage of a recent approach in which cells in a dish are coaxed to grow into tissue organoids, which are about the size of a lentil and have a three-dimensional structure. These techniques can then capture certain aspects of the tissue in question, including whether it is healthy or growing abnormally, better than standard techniques of growing cells in two-dimensional layers.
The team has now shown that amniotic fluid samples taken during pregnancy contain fetal cells capable of forming organoids of lung, kidney and small intestine tissue.
Studying organoids made from cells from fetuses known to have congenital disease may be able to provide doctors with more information about its specific form, severity and how to treat it.
In the study, the team created organoids for 12 fetuses with CDH, whose abdominal organs pushed up into the chest, preventing the left lung from growing normally. This condition can be treated while the fetus is in the womb by pushing a balloon into the lungs to expand them, helping them develop better.
The researchers created lung organoids from fetuses before and after balloon treatment. They saw some signs that the organoids produced after the treatment behaved more like healthy lung tissue than those produced before, suggesting the treatment was successful.
Organoid technology can therefore be used to monitor whether a treatment is working, and to gauge whether treatment is needed in the first place, since doctors only use this intervention in the most severe cases.
“This has great potential for functional diagnostics,” DeCoppi said. “We know how to diagnose based on imaging, but sometimes there can be multiple (severities of conditions). We want to provide better prenatal diagnostic tools.”
“If you can classify a disease as mild, moderate or severe, that’s a great achievement,” said Cecilia Gsestrom at Karolinska Institute in Stockholm, Sweden.
Holm Schneider The approach also suggests that organoids could one day be converted into mature tissue for implantation into babies after birth, for example if part of the intestine is missing, said the University Hospital of Erlangen in Germany. “If you could engineer a gut-like structure that these children could use after birth, you would be in a much better position,” he said.
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