What if the placenta could teach us how to redirect chronic inflammation towards tissue repair?
Our study, published in the Journal of Extracellular Vesicles, focuses on extracellular vesicles (EVs) released by extravillous trophoblasts (EVTs), specialised cells that play a central role in early placental development. These tiny biological packages carry proteins, lipids and RNA from one cell to another, acting as messengers that can reshape the behaviour of recipient cells.
Using a stable human trophoblast model, we generated placenta-derived EVs (PEVs) and investigated their effects on circulating human monocytes, key drivers of inflammatory responses. The results were striking: PEVs reprogrammed monocytes towards an immunomodulatory, inflammation-resolving state. Integrated molecular analyses revealed coordinated changes in immune and metabolic pathways, suggesting that these EVs do not simply suppress inflammation. Rather, they can redirect immune-cell function towards a state more compatible with tissue homeostasis and repair.
We then asked whether this effect could also be observed in a chronic inflammatory disease. We tested monocytes from patients with recessive dystrophic epidermolysis bullosa (RDEB), a rare genetic disorder characterised by severe tissue damage and persistent inflammation. Remarkably, PEVs also modulated the inflammatory state of these patient-derived cells, promoting changes consistent with a restoration of immune balance.
But could this biology be translated into a reproducible source of immunomodulatory EVs?
Primary first-trimester trophoblasts are invaluable for studying placental biology, but their limited availability and donor-to-donor variability make them difficult to use as a consistent source of EVs. Our stable trophoblast model provides an off-the-shelf and reproducible source of PEVs. Importantly, their molecular cargo closely resembles that of EVs derived from primary first-trimester human trophoblasts, supporting the biological relevance of the model.
This combination of placental biology, immune reprogramming and reproducible PEV production opens an interesting translational perspective. Rather than simply blocking inflammation, could we learn to redirect it towards resolution and tissue repair?
Our findings do not yet demonstrate a treatment for chronic inflammatory disease. They reveal something potentially more fundamental: the placenta naturally produces extracellular messages capable of reprogramming inflammatory immune cells—and these messages remain active outside pregnancy, even in cells from patients with chronic inflammatory disease.
The placenta may therefore be more than a model of maternal–fetal immune tolerance. It could provide a blueprint for restoring immune balance and redirecting inflammation towards tissue repair.
https://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jev2.70315