Pregnancy is an extremely complex biological process, the details of whose initial development are still unexplored. Detailed study of the early stages of the placenta is necessary because its functioning ensures normal fetal growth and directly determines the course of pregnancy.
Existing Obstacles:
Procedural Risk: Taking samples from an early pregnancy is risky and ethically unacceptable.
Information Deficit: The post-partum (fully mature) placenta cannot reflect the course of early pathological processes.
Species Differences: Animal models, despite some benefits, cannot provide the possibility of accurately simulating pregnancy complications due to significant species differences.
The creation of placental organoids is an effective way to overcome these challenges and represents an ethical, controlled, and highly reproducible research platform.
Scientists used an innovative combination of 3D bioprinting and a synthetic matrix for the growth of placental cells. The resulting structures successfully simulate the early development of the placenta in a laboratory environment. The main advantage of the synthetic polyethylene glycol (PEG) matrix is that, unlike gels of animal origin, it creates a controlled and stable environment. The research discussing this groundbreaking discovery was published in Nature Communications.
How Was the Mini-Placenta Created?
Led by Associate Professor Lana McClements and Dr. Claire Richards at the University of Technology Sydney (UTS), the research team used a synthetic matrix to mimic the uterine environment. For the study, scientists used first-trimester placental cells—the trophoblastic cell line (ACH-3P). With the help of 3D bioprinting, these cells were used to create organoids that contained the three main placental cell types: Cytotrophoblasts, Extravillous Trophoblasts (EVTs), and Syncytiotrophoblasts (STBs).
It is important to note that the matrix (gel scaffold) actively influenced the cellular environment: the synthetic matrix promoted the development of EVTs (cells responsible for the implantation of the placenta into the uterine wall), while the older, animal-derived gel primarily contributed to the formation of Syncytiotrophoblasts (cells that ensure metabolism).
Furthermore, scientists were able to imitate the dynamic architecture of the placenta in an innovative way. Removing the organoids from the matrix and suspending them in culture (placing them in a liquid state) caused a change in their internal-external polarity. This further facilitated the process of Syncytiotrophoblasts forming the outer surface of the early placenta.
The scientists were also able to simulate preeclampsia (a dangerous hypertensive disorder) on the organoids using inflammatory signals. The research showed that inflammation hinders the growth of the organoid and weakens the formation of the Syncytiotrophoblast (the cell needed for metabolism). Aspirin and metformin, medications often used to treat preeclampsia, did not help the organoids correct the inflammatory damage at the tested doses. This result unambiguously shows the urgent need for developing more targeted and effective therapies.
Molecular Precision and Medical Potential
In-depth analysis of cells and proteins (proteomic and transcriptomic studies) confirmed that the artificially created organoids are identical at a molecular level to actual, early maternal-fetal tissue. Thanks to this precision, the model showed the expression of important placental genes, including Metallothionein 2A (MT2A); MT2A is crucial for protecting the fetus from toxins and regulating the course of pregnancy. Moreover, the model allowed for the identification of clear cell populations and their stages of maturation.
In addition, the chemical and physical properties of the synthetic PEG matrix can be adjusted to accurately model various uterine conditions, including changes in tissue stiffness during pregnancy or pathologies.
Thanks to the bioprinting technology, the cells and matrix were automatically and accurately arranged, which made the models identical and reusable. This capability is crucial for future large-scale drug testing and will significantly improve methods for predicting, preventing, and treating complications such as preeclampsia, spontaneous abortion, and fetal growth restriction.
In the future, researchers plan to further refine the model: maternal immune and stromal (connective) cells will be added to the organoids to better simulate different stages of pregnancy. By changing the stiffness and chemical signals of the matrix (gel scaffold), scientists will study how the physical environment affects placental health.
This multifunctional model ultimately allows us to study one of the most important, yet previously difficult to study, stages of life.
Source: nature
