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Study shows promise of creating mini kidneys for personalised prenatal care

06 March 2024

In a recent study, published in Nature Medicine and part-funded by Kidney Research UK, a team of researchers from University College London and Great Ormond Street Hospital have shown the promise of a pioneering method to predict and potentially treat kidney problems before birth. 

Predicting the severity of kidney problems before birth

Some children are born with kidney disease; this is often due to changes in their genetic material (DNA). Advances in genetic testing and imaging technologies mean that doctors are often able to diagnose kidney problems during pregnancy, but conditions will often present differently in different people, and it is difficult to predict how severe any problems will be or to explain to parents what the likely impact on their child’s life will be.  

In some cases, there are treatments available before birth, but it is difficult to know which patients will benefit most from these. Finding a way to recreate how the tissues develop would pave the way for personalised treatments for babies with developmental kidney problems. 

Do organoids hold the answers?

Organoids are miniature versions of organs, such as kidneys, that can be grown in laboratories allowing researchers to study what changes occur during different diseases and developmental problems. Organoids also allow researchers to test potential new treatments. 

Until now, there hasn’t been a way to grow organoids from developing babies while continuing the pregnancy.  

Creating organoids from amniotic fluid

Developing human babies are cushioned within the womb in a liquid called amniotic fluid. In this study, the team have developed a novel method of growing organoids from cells that have passed from the developing baby into this fluid. Samples of amniotic fluid can be removed in a process called amniocentesis, which is already routinely performed during pregnancy to test for genetic conditions.  

The team collected amniotic fluid from 12 pregnancies and managed to extract different types of stem cells (special cells from the body that can transform into different cell types) from the lungs, kidneys and intestines; they were then able to grow organoids that that mimicked the babies’ developing organs. This is the first time that organoids have been grown from human stem cells during an active pregnancy. 

This research was supported by the National Institute for Health and Care Research and the European Commission Horizon 2020 Programme. Dr Mattia Gerli and Kidney Research UK-funded PhD student Kylin Yunyan Sun in their team, carried out the kidney section of this work. Mattia said: “The organoids we created from amniotic fluid cells exhibit many of the functions of the organs that they represent. They will allow us to study what is happening during development in both health and disease, which is something that hadn’t been possible before. We know so little about late human pregnancy, so it’s incredibly exciting to open up this new area of medicine.” 

Professor Paolo de Coppi, senior author of the study from UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, said: “When we meet families with a prenatal diagnosis, we’re often unable to tell them much about the outcome because each case is different. We’re not claiming that we can do that just yet, but the ability to study functional prenatal organoids is the first step towards being able to offer a more detailed prognosis and, hopefully, provide more effective treatments in future.” 

Kidney organoid
Image captured by Kylin Yunyan Sun: Amniotic fluid-derived kidney organoid

An example of this method in action

As an example of how this technique could be used to manage the personalised care of conditions that babies are born with, the team worked with researchers at KU Leuven in Belgium to study the development of babies with Congenital Diaphragmatic Hernia (CDH), a condition where a hole in the diaphragm means that organs from the abdomen (such as the intestines) can move into the chest, affecting breathing and lung development.  

There is a treatment available for babies with CDH in the womb that improves lung development and prepares them for surgery after birth. The team compared lung organoids from babies with CDH, both pre- and post-treatment with healthy babies. They saw important differences between the healthy and pre-treatment CDH organoids, but the post-treatment CDH organoids had more similarities with the healthy ones, giving an estimate of how effective the treatment is.  

Getting a head-start on conditions present at birth: what could this mean for patients?

This new technique would allow researchers to develop patient-specific organoids of lung, small intestine and kidney during pregnancy in a matter of weeks, enabling them to understand how severe the developing baby’s condition will be and also offering the opportunity to test potential treatments. 

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