Tokyo Medical and Dental University (TMDU) scientists create a novel in vitro model to advance research on the placental barrier.
The human placenta plays a crucial role during pregnancy, serving as a protective barrier for the developing fetus. However, certain drugs can breach this barrier and potentially harm the fetus. To further understand placental biology and drug toxicity, researchers at Tokyo Medical and Dental University (TMDU) have successfully developed a trophoblast stem (TS) cell-based organoid model of the placental barrier. This innovative model offers new opportunities for studying placental physiology and evaluating the transfer rates and toxicity levels of various compounds.
Challenges in Studying Placental Physiology
The structural nature of the placental villi, critical for its function as a barrier, has posed challenges for researchers attempting to replicate placental physiology in laboratory experiments. Existing methods, including cell lines, have proven inadequate. Maintaining primary placental cells in culture has also been difficult. To overcome these limitations, the TMDU team aimed to create an effective in vitro model of placental villi using TS cells.
Generating Trophoblast Organoids
The researchers first generated trophoblast organoids, a three-dimensional cell model that mimics the structural and biological details of an organ more effectively. They tested three types of culture medium and determined the optimal conditions for forming spherical organoids. The outer layer of the organoids, composed of syncytiotrophoblasts, displayed the desired barrier function.
Establishing a Flatter Organoid Model
Building upon the culture conditions of the spherical organoids, the team developed flatter organoids with a column-type container. This design allowed for easy assessment of compound translocation through the barrier layer. The researchers employed various methods to confirm the barrier integrity and maturation levels of the plane organoids, ensuring the robustness of the system. The model’s permeability coefficients were also examined to assess how different compounds crossed the barrier.
Advancing Placental Biology and Drug Development
The TS cell-based organoid model addresses previous difficulties in studying placental physiology in the laboratory. This innovative tool not only provides insights into the development of the placenta but also enables the evaluation of transfer rates and toxicity levels of various compounds. This knowledge is crucial for drug development, as it helps researchers avoid damaging the placenta or harming the fetus.
A Promising Future for Placental Research
By utilizing the TS cell-based organoid model, scientists can gain a better understanding of placental biology and potential drug toxicity. The model’s ease of culture and evaluation through microscopic observation make it a valuable tool for future research. This breakthrough could lead to advancements in pregnancy-related studies and contribute to the development of safer medications for pregnant women.
The development of a trophoblast stem cell-based organoid model of the placental barrier by researchers at TMDU opens new avenues for studying placental biology and evaluating the effects of various compounds on the developing fetus. This innovative model provides a more accurate representation of the placental barrier and offers insights into drug transfer rates and toxicity levels. As scientists continue to explore the intricacies of placental physiology, this breakthrough will undoubtedly contribute to safer drug development and improved understanding of pregnancy-related conditions.