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Scientists have for the first time grown organoids from foetuses in late pregnancy, in a breakthrough that could make it much easier to monitor and treat congenital conditions before birth.
Researchers at Great Ormond Street Hospital and University College London extracted stem cells from the amniotic fluid that surrounds the foetus during pregnancy. These cells developed into organoids — miniature human organs — about 1mm across that showed the functional characteristics of specific tissues: kidneys, lungs and small intestine.
The discovery that a sufficient number of stem cells leak into the fluid for scientists to extract and grow into organoids will advance the development of prenatal treatments that ensure healthy births, said researchers in the study.
Organoids derived from stem cells are one of the fastest-growing fields in biomedical research. From mini-guts to mini-brains, tissues are being used in applications ranging from screening experimental drugs to assessing the treatment of individual patients. But more research will be needed before organoids can replace or supplement failed organs.
The foetal findings, which were published in Nature Medicine on Monday, “will allow us to study what is happening during development in both health and disease”. said Mattia Gerli, stem cell biologist at UCL. “We know so little about late human pregnancy, so it’s incredibly exciting to open up new areas of prenatal medicine.”
Cells were extracted from 12 foetuses in the experiment. To demonstrate the practical application of the technology, the scientists worked with colleagues at KU Leuven, a university in Belgium, to model congenital diaphragmatic hernia. CDH is a frequently fatal disease in which the baby’s intestine and liver push into the chest through a hole in the diaphragm, exerting severe pressure on the lungs.
Lung organoids grown from foetuses with CDH showed characteristic differences from those from healthy pregnancies or from foetuses that had been successfully treated for the condition with prenatal surgery in the womb.
“This is the first time that we’ve been able to make a functional assessment of a child’s congenital condition before birth, which is a huge step forward,” said Paolo de Coppi, a paediatric surgeon at Great Ormond Street Hospital, adding that diagnosis was normally based on magnetic resonance or ultrasound imaging and genetic analyses.
The technique could be extended to other congenital conditions affecting the intestines, kidneys or lungs, he said, though these had not yet been tested experimentally.
It is illegal to take cells directly from a living foetus in the later stages of pregnancy in many countries, including the US and UK, whereas amniotic fluid is frequently sampled for prenatal diagnosis.
The organoids took up to four weeks to develop after the stem cells were extracted from amniotic fluid, said Gerli. That gives plenty of time for them to be analysed and the results applied to diagnose and treat congenital abnormalities.
The researchers cautioned that the technology would need to be validated with data from larger studies, “Amniotic fluid organoids have a lot of clinical potential but they are not yet ready for the clinic, nor can they be used at this stage to treat conditions,” said De Coppi.
The process did not depend on expensive specialised equipment, potentially allowing it to be applied extensively in maternity hospitals, Gerli said: “It requires very basic cell culture skills that are already widely available.”
Roger Sturmey, a professor of reproductive medicine at Hull university who was not involved in the project, said the research paved the way for further studies on “how key organs are formed and perform their function in the developing foetus during pregnancy, without the need for tissue extracted directly from a foetus — which is typically only available following termination of a pregnancy”.
The UCL/GOSH project to make tissue-specific foetal organoids differs from research taking place in other labs to create complete models of early embryos from stem cells.
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