The protective sac that surrounds developing babies in the womb harbors remarkable regenerative powers that scientists are only beginning to understand. Now, researchers have created the first comprehensive map of the human amnion during early pregnancy, revealing cellular secrets that could transform regenerative medicine.
The amnion is the innermost membrane surrounding a developing fetus, creating the fluid-filled cavity that cushions and protects the baby throughout pregnancy. But this tissue is far more than just a protective barrier – it has unique properties that make it valuable for treating wounds, burns, and other injuries.
"The amnion not only physically protects the embryo but also secretes essential hormones and cytokines that support embryonic development," says Magdalena Zernicka-Goetz at the California Institute of Technology, who led the study.
To understand how the amnion develops its special properties, Zernicka-Goetz and her colleagues analyzed over 14,000 individual cells from human amnion samples collected between 5 and 9 weeks of pregnancy. Using cutting-edge single-cell sequencing technology, they identified distinct cell types and tracked how they change over time.
The team discovered that amnion cells undergo dynamic transformations during early pregnancy, with some epithelial cells transitioning into mesenchymal cells – a process that helps the tissue remodel and repair itself. They also found immune cells within the amnion that express factors like MIF and SPP1, which suppress immune responses.
"These immunosuppressive factors provide a possible explanation for the amnion's capacity to inhibit immune responses," says Zernicka-Goetz.
This property is particularly valuable in clinical applications, as amnion grafts are less likely to be rejected by patients' immune systems.
The researchers identified BMP4 as a critical signaling molecule driving amnion development. When they treated stem cells with BMP4 in the lab, the cells began expressing amnion markers, suggesting potential ways to generate amnion-like tissue for therapeutic use.
Perhaps most intriguingly, the team's analysis revealed that different laboratory methods for creating amnion-like cells from stem cells actually recapitulate different stages of natural amnion development. This finding could help researchers optimize protocols for generating amnion tissue for specific medical applications.
The amnion's combination of low immunogenicity, anti-inflammatory properties, and regenerative potential makes it attractive for various therapeutic applications. Amnion membranes are already used clinically to treat chronic wounds, burns, and eye injuries, but understanding the cellular basis of these properties could lead to more targeted and effective treatments.
"This cellular map serves as a valuable resource for future functional studies on amnion development and potential therapeutic applications," says Zernicka-Goetz.
The findings could also help explain why some pregnancies experience premature rupture of membranes, a serious complication that can lead to preterm birth. By understanding normal amnion development, researchers may be able to identify what goes wrong in these cases and develop preventive treatments.
Journal reference: Nature Cell Biology DOI: 10.1038/s41556-025-01696-9