They create mini-organs from fetal cells to study malformations

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For the first time, they develop organoids from stem cells present in the amniotic fluid, an advance that can help study the development of the fetus in the womb and understand the causes of congenital malformations and how to prevent and treat them.

A multidisciplinary team of researchers has managed to grow various types of organoids from cells found in the amniotic fluid, an advance that according to the authors of the work could contribute to a better understanding of the last stages of fetal development during pregnancy and facilitate the prevention and treatment of congenital malformations. The findings have been published in Nature Medicine.

The organoids were created from lung, kidney and intestine cells recovered from the amniotic fluid that surrounds and protects the fetus in the womb. It is the first time that organoids of this type have been produced from untreated cells present in the fluid, opening an unprecedented avenue to knowledge about the causes and progression of malformations, which affect 3-6% of babies worldwide. world.

Dr. Mattia Gerli, a stem cell researcher at University College London (UCL), explained that fetal organoids, which measure less than a millimeter wide, would allow scientists to study fetal development in the womb “both under of health, as of illness”, something that until now had not been possible. Because organoids can be created months before a baby is born, scientists believe they could lead to more personalized interventions by helping doctors diagnose defects and determine the best way to treat them.

Detect and act on congenital malformations before birth

Organoids are small conglomerates of cells that mimic the characteristics and functions of larger tissues and organs and are used by scientists to study how organs grow and age, how diseases progress, and whether drugs can reverse any damage they have suffered.

In the paper published in Nature Medicine, Gerli and Prof. Paolo de Coppi, a fetal surgeon at the Great Ormond Street Institute of Child Health, describe how they analyzed amniotic fluid from 12 pregnant women as part of their routine diagnostic tests. Most of the cells in the amniotic fluid were dead, but a small fraction turned out to be stem cells for the formation of the baby’s lungs, kidneys and intestines. The researchers found that they could grow these into three-dimensional organoids by injecting them into gel droplets.

To explore how organoids could be used, the team created lung organoids from cells from unborn babies with a condition called congenital diaphragmatic hernia, or CDH. Babies with CDH have a hole in the diaphragm, the dome-shaped muscle under the lungs that drives breathing. The hole allows the organs in the abdomen to push up into the lungs and prevent their growth.

Comparison of organoids from babies with CDH before and after treatment showed substantial differences in their development, pointing to a clear benefit of the treatment. “This is the first time that we have been able to do a functional evaluation of a congenital condition in a child before birth,” De Coppi highlighted.

This same approach could help investigate other congenital conditions such as cystic fibrosis, which causes mucus buildup in the lungs, and malformations in the kidneys and intestine. Additionally, drugs that help alleviate congenital disorders could be tested on organoids before being given to babies, De Coppi said.

Iván Fernández Vega, university professor linked to the Central University Hospital of Asturias, scientific director of the Biobank of the Principality of Asturias (BioPA) and coordinator of the Organoid Hub of the National Platform of Biobanks and Biomodels of the ISCIII, who has not participated in the study, considers it very interesting from a scientific and social point of view, as he told SMC Spain: “In prenatal research, the creation of fetal organoids had been carried out from fetal tissues collected postmortem through biobanks and under restrictions ethical-legal issues that can hinder the investigation. This article describes a technique for the derivation of fetal epithelial organoids from different tissues from fetal fluids that make up the amniotic fluid, through minimally invasive sampling.

“We describe how organoids of the small intestine, renal tubules and lungs are expandable and can functionally mature with great potential for regenerative medicine and personalized disease modeling. This advance would allow the study to be carried out in ongoing pregnancies, being able to provide ad hoc solutions in the future, with real-time analysis during pregnancy, which could potentially lead to more personalized and effective treatments,” concludes the expert.

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