Amniotic fluid contains living fetal cells, and researchers will now grow these into miniature organs to test treatments for rare diseases before a baby is born. Congenital conditions such as spina bifida, cystic fibrosis, and polycystic kidney disease are diagnosed during pregnancy, but doctors have few ways to predict how severely a baby will be affected or to test whether a drug might help before birth. This project fills that gap by creating a detailed cellular map of diseased amniotic fluid and growing organoids—tiny, three-dimensional tissue models—from the same fluid samples. If successful, the organoids could serve as personalised test beds for drug screening and treatment response during pregnancy. The team will also compare laboratory findings with clinical outcomes such as survival and disease severity, aiming to identify patterns that predict how a baby will fare. This could improve counselling for families and enable early, tailored interventions. The work is exploratory and fundamental, but it opens a largely unexplored field: personalised disease modelling before birth.
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This project aims to advance our understanding of congenital diseases, conditions that are affecting babies at or before birth. To do so, we will study the fetal cells present in the amniotic fluid (AF), the protective liquid surrounding the fetus during pregnancy. We already established a control cellular map of the healthy AF. Our goal with this project is to create a single-cell atlas of diseased AF, to enable detailed comparison between cellular composition of healthy and disease-affected pregnancies. The objective of this, is to uncover disease-related changes in the populations of AF cells. These changes could be used before birth as biomarker, to track and predict the outcomes of a number of congenital diseases. Moreover, we will derive and study mini-organs (or organoids) from diseased AF cells, through a protocol recently developed by my team. Being derived before the baby is born, these organoids could serve as 3D models to study the course of congenital diseases and test treatments during pregnancy. This project will focus on rare, but impactful conditions such as myelomeningocele (MMC), cystic fibrosis (CF) and polycystic kidney disease (PKD) for which AF samples are already accessible to my team. The proposal consists of three specific aims. First, we will collect AF from affected pregnancies and use single-cell biology techniques to study their gene and protein expression. This will allow comparing cell types and amounts present in patients vs. controls, to uncover specific features of our target diseases. Second, we will use AF cells from the same patients to grow AF organoids (AFO). As we have recently shown for congenital diaphragmatic hernia (CDH), another congenital condition, AFO can be used to study the effect of these diseases on organ development. Here we will test in CF AFO the activity of CFTR, the gene affected by the disease. Moreover, we will assess cysts formation in PKD AFO as hallmark of the condition. Finally, our system will be used to test AFO’s as in vitro model for the response to treatments. Ultimately, my team’s research overall, aims to translate our cellular and molecular data into the clinic. The third part of the project aims at correlating our AF cell maps, and AFO data with the patients’ clinical outcomes. We will compare our laboratory results with the patients’ clinical prenatal imaging, survival information and disease severity. The idea is to identify patterns connecting our laboratory observations to the actual effect of the diseases on these babies. If successful, our newly developed techniques could become powerful tools for early severity prediction. Our models could find use in drug screening and to test response to treatment before birth. Moreover, this will provide better estimate on how babies might be affected by these conditions, to offer better counselling to the affected families. Ultimately, this exciting project will enable the first steps to explore personalised disease modelling before the baby is born, a largely unexplored field.
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