Mini-organs created from amniotic fluid cells

A team of researchers from KU Leuven, UZ Leuven, University College London and the Great Ormon Street Hospital for Children were able to create “mini-organs”, called organoids, from human stem cells from amniotic fluid from an active pregnancy. These could facilitate the diagnosis and treatment of congenital conditions before birth.

Their discovery was presented in the journal Nature MedicineMarch 4, 2024.

Organoids created from amniotic fluid stem cells

Until now, scientists have created organoids mainly using adult stem cells, because the collection of fetal samples is highly regulated, or even prohibited in some countries. However, these restrictions limit the usefulness of mini-organs for studying normal human development as well as congenital diseases and their treatments. The European team thus had the idea of ​​cultivating organoids from stem cells present in amniotic fluid. “Since the fetus would not be touched during the collection process, sampling restrictions would be overcome and the cells would carry the same biological information as those of the child”explain the authors in the UCL press release.

In their work, they extracted stem cells from samples of amniotic fluid taken as part of routine diagnostic tests from 12 pregnancies. They then used single-cell RNA sequencing to identify which tissues the samples came from. Results: The stem cells came from the lungs, kidneys and intestine. They were then used to create organoids and had the same functional characteristics as the original tissues.

Dr Mattia Gerli, first author of the study from UCL Surgery & Interventional Science, explains: “The organoids we created from amniotic fluid cells exhibit many of the functions of the tissues they represent, including gene and protein expression. They will allow us to study what happens during development , in both health and disease, which was not possible before. We know so little about the final weeks of a human pregnancy, so it’s incredibly exciting to open up new areas of medicine prenatal.”

Mini-organs: helping to better diagnose congenital diseases

To evaluate how organoids could be used in the treatment of congenital diseases, the team followed the development of fetuses with congenital diaphragmatic hernia (CDH). This pathology is characterized by the absence of closure of the pleuroperitoneal canal between 9 and 10 weeks of pregnancy leading to an ascension of the abdominal viscera into the thoracic cavity. This puts pressure on the lungs and hinders their growth.

Doctors created organoids from babies with CDH before and after treatment as well as healthy babies from cells taken from amniotic fluid. “As expected, there were significant developmental differences between healthy and pre-treatment HDC organoids. But organoids in the post-treatment HDC group were much closer to healthy organoids, providing an estimate of treatment effectiveness at the cellular level .”

Professor Paolo de Coppi, lead author of the study from the UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, explains: “This is the first time that we are able to carry out a functional assessment of the congenital state of a child before birth. This represents a major step forward for prenatal medicine. The diagnosis is normally based on the imaging such as ultrasound or MRI and genetic analyses.”

“When we meet families who have received a prenatal diagnosis, we are often unable to tell them much about the outcome, because each case is different. We do not pretend that we can do this yet, but the capacity “Studying functional prenatal organoids is the first step toward being able to offer a more detailed prognosis and hopefully provide more effective treatments in the future.”adds the expert.

Indeed, for researchers, these mini-organs could also help evaluate the effectiveness of new treatments against congenital diseases.