Researchers develop model to assess human placental barrier biology

During pregnancy, the human placenta plays several essential roles, including producing hormones and processing nutrients and wastes. It also serves as a barrier to protect the developing fetus from external toxic substances. However, some medications can still break down the placental barrier. In a study published in Natural communicationsA team led by researchers at Tokyo Medical and Dental University (TMDU) developed an organoid model of the placental barrier based on trophoblast stem (TS) cells to support further biological research.

The villi of the human placenta help form the barrier and are surrounded by a layer of cells called trophoblasts. Because the structural nature of villi is essential to their function, cell lines and other methods used to reproduce placental physiology in laboratory experiments have proven inadequate. Primary placental cells are also difficult to maintain in culture. Therefore, the TMDU group aimed to develop an effective in vitro model of placental villi using TS cells.

“TS cells have the ability to differentiate into all kinds of placental cells made up of the human placenta,” explains Dr. Takeshi Hori, lead author of the study. “However, it has been difficult to create a barrier model using TS cells.”

The team first generated trophoblast organoids, a type of three-dimensional cellular model that can more effectively mimic the structural and biological details of an organ. After testing three types of culture media, they determined the optimal conditions to promote the formation of spherical organoids.

“The outer layer of the organoid contained a single layer of cells called syncytiotrophoblasts,” explains lead author Dr. Hirokazu Kaji. “This layer effectively displays the barrier function that we sought to mimic with this model.”

Based on the culture conditions of spherical organoids, the researchers established flatter organoids with a column-like container to easily evaluate the translocation of compounds across the barrier layer. Researchers used various methods to confirm the barrier integrity and maturation levels of planar organoids and to ensure the robustness of the system. Their analysis also showed that the model could be used to assess how well different compounds could pass through the barrier, including looking at permeability coefficients.

“Using organoids as a model of the placental barrier will help scientists better understand general placental biology and potential drug toxicity,” says Dr. Hori. “We also designed our model so that cells can be easily cultured and assessed by microscopic observation.”

The TS cell-based organoid model generated in this study effectively resolves many of the difficulties that have previously hampered laboratory assessments of placental physiology. This will be a useful tool not only for elucidating the details of the development of this organ, but also for assessing the transfer rates and toxicity levels of various compounds. In the drug development process, this will be essential to avoid damage to the placenta or fetus.