Scientists from University College London (United Kingdom) have published research in Nature Medicine in which fetal stem/progenitor cells were obtained from amniotic fluid and grown in the laboratory to give rise to organoids. These are three-dimensional models of miniature organs on which a multitude of in vitro studies can be carried out. This is the first time organoids have been cultured directly from cells taken from ongoing pregnancies.

The cells obtained were epithelial cells of fetal gastrointestinal, renal and pulmonary origin, from which they managed to form organoids that manifested the self-identity of the small intestine, renal tubules and lungs, respectively. The medical interest of these experiments lies in the potential of these organoids to be used in research on diseases that develop in the fetus during pregnancy, which could open a new door in the field of fetal medicine in the future, making it possible to personalize the treatment of fetuses with congenital diseases.

Organoids are generally grown from cells taken from biopsies, which are reprogrammed in the laboratory to become stem cells, with the potential to develop organoid models. However, in the case of fetuses this implies that the fetus has been aborted. Therefore, researchers have limited access to fetal cells, which are also limited to the earliest stages of gestation. The new published study overcomes this serious ethical problem and also allows researchers to study fetal tissue from later stages of pregnancy.

The researchers grew organoids from cells present in amniotic fluid collected from 12 pregnancies between 16 and 34 weeks of gestation. The samples were obtained by amniocentesis, a technique that consists of inserting a needle into the uterus and extracting amniotic fluid and is generally performed until the 20th week of gestation. Or through amniotic drainage to eliminate excess fluid, which is carried out until the 34th week of gestation.

Credit: Gerli, M.F.M., Calà, G., Beesley, M.A. et al. Nat Med 30, 875–887

These are standard procedures during prenatal care, so “they give us the opportunity to take amniotic fluid without any additional procedures”, explains study co-author Paolo De Coppi, a pediatric surgeon at Great Ormond Street Hospital in London. All samples were taken from people who underwent one of the study’s independent procedures.

The researchers first isolated individual cells from the samples and characterized their origins. Most were epithelial cells, which cover the surface of organs. Organoids were cultured from three organs: the small intestine, kidneys and lungs. The cells were transferred to gel medium to multiply and grow. Each organoid expressed the genes and proteins of the organ from which it originated.

In addition to the tissue-like organoids, the researchers also modeled congenital diaphragmatic hernia (CDH), a disorder in which the diaphragm does not develop properly, using cells from samples affected by the disorder. Therefore, the procedure may be useful to study specific fetal pathologies. However, at the moment there are some limitations.

Thus, only the epithelial tissue of the three organs has been successfully converted into organoids using this technique. More complex congenital diseases usually affect multiple layers of tissue, so they could not be modeled. Nor can organs that do not shed cells into the amniotic fluid, such as the brain or heart, be modeled.

Despite the still existing limitations and the need to carry out additional studies before transferring these advances to the clinic, organoids derived from fetal stem cells present in the amniotic fluid open the door to the development of new therapeutic tools and personalized regenerative medicine strategies for the fetus. Likewise, it is very positive that these investigations do not require the handling of cells from aborted fetuses, which represents an important ethical advantage over previous procedures for generating fetal organoids.

Lucía Gómez Tatay

Bioethics Observatory -Institute of Life Sciences

Catholic University of Valencia

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