They create mini-human organs from fetal cells, allowing them to treat diseases before birth.

Organoids are three-dimensional microtissues derived from stem cells that recreate in vivo human organs such as the lungs, liver or brain. For several years now they have become valuable tools for analyzing their functioning, both when they are healthy and when they are affected by any disease.

Current methods for obtaining these structures for pregnancy simulations—mostly from postmortem fetal tissue—have legal and ethical implications. Moreover, they are usually only available 20-22 weeks after conception.

This fact has limited studies of developmental and congenital changes (those that affect the formation of a child’s body parts or activity) and has emphasized the need to create new in vitro models specific to each patient.

Now, a study published in the journal Nature Medicine shows that organoids from several tissue types can be obtained from cells collected from amniotic fluid samples without the need for pregnancy termination, optimizing the understanding of later phases of pregnancy and the treatment of these congenital diseases. anomalies.

The work, led by scientists at University College London in the UK, suggests that these complex cell models could be grown from stem cells trapped in the amniotic fluid that surrounds and protects the fetus in the womb. it grows during pregnancy.

“This is the first time that organoids have been grown from human stem cells during an active pregnancy. Since the baby will not be touched during the extraction process, sampling restrictions will be overcome and these mini-organs will also preserve the baby’s biological information.” “, explains SINC Paolo De Coppi, the main co-author of the study.

“Congenital malformations are diagnosed using a combination of tests, including imaging (ultrasound and MRI) and genetics,” adds De Coppi, “so organoids open up the possibility of additional functional testing.”

Lung organoids from amniotic fluid. Red color indicates a lung stem cell marker used to determine tissue type. / Giuseppe Cala, Paolo De Coppi and Mattia Gherli

Promotion of prenatal medicine

In this study, researchers extracted and characterized living cells from amniotic fluid samples collected from 12 pregnancies as part of a series of routine diagnostic tests such as amniocentesis.

They then used single-cell RNA sequencing to determine which tissues these stem cells came from. Thus, they isolated epithelial cells of pulmonary, renal, and gastrointestinal origin, which they used to culture organoids with the functional characteristics of lung, kidney, and intestine, respectively.

“The organoids we created from amniotic fluid cells have many of the functions of the tissues they represent, including gene and protein expression,” says Mattia Gerli, first author of the study.

“They will allow us to study what happens during development,” he continues, “something that was previously impossible. We know very little about the last stage of human pregnancy, so it is incredibly exciting to discover new areas of prenatal medicine.” “

Congenital malformation research

To evaluate how organoids could be used to treat congenital conditions, the team, in collaboration with experts from the Catholic University of Louvain (Belgium), analyzed the development of children with congenital diaphragmatic hernia (CDH), a condition in which the diaphragm causes organs such as the intestines and liver to move into the chest, putting pressure on the lungs and preventing healthy growth.

Organoids from infants with CDH were compared with organoids from healthy controls to examine the biological characteristics of each group. As expected, there were significant differences in mini-organ development before and after treatment. However, those who had abnormalities after treatment were much more similar to healthy people, which allows us to evaluate the effectiveness of treatment at the cellular level.

“For the first time, we can perform a functional assessment of a baby’s congenital condition before birth, which is a big step forward for prenatal medicine. Diagnosis is usually based on imaging studies such as ultrasound or MRI, as well as genetic testing,” says De Coppi.

Intestinal organoids from amniotic fluid that have a characteristic structure. The blue areas are proliferating intestinal stem cells that mature into more specialized absorptive intestinal cells (red areas). / Giuseppe Cala, Paolo De Coppi and Mattia Gherli

Work restrictions

The scientists note that their findings may make it possible to obtain primary fetal organoids autologously (that is, they are obtained from the same person who receives them) during an ongoing pregnancy, which could allow the development of advanced prenatal models and personalized treatments, as well as optimized advice to parents .

“When we meet with families with a prenatal diagnosis, we often cannot tell them much about the outcome because each case is different. We don’t intend to do that yet, but being able to study functional prenatal organoids is a first step in providing more detailed prognosis and hopefully leading to more effective treatments in the future,” explains De Coppi.

In fact, they note that more research is needed to confirm the translational impact of these findings. “Some of the limitations are that amniotic fluid-derived organoids are not yet ready for the clinic and cannot be used at this stage to treat diseases,” Gurley told SINC.

“In addition, we can model the epithelial compartment of only a few tissues: lung, kidney and intestine. And at the moment they are not an alternative to organoids obtained from pluripotent stem cells, and do not replace the production of cells and organoids from ready-made tissues.” “concludes the researcher from University College London.

Link:

Mattia Gerli et al. “Single-cell prenatal production of primary fetal epithelial organoids from human amniotic fluid and tracheal fluids.” Natural Medicine 2024