New study: Enhancing Immune Modulation with “trained” MSC-EVs
One of the key research priorities of the RESTORE VISION project is improving the effectiveness of novel therapies including Mesenchymal Stromal Cell-derived extracellular vesicles (MSC-EVs) for treatment of rare eye diseases.
Mesenchymal stromal cells (MSCs) are showing great promise in treating conditions where the immune system is overactive, like autoimmune disorders. Rather than using the whole MSCs, scientists are focusing on the tiny particles they release—called extracellular vesicles (EVs)—which can have similar effects or even outperform whole MSCs. To make MSCs (and EVs) even more therapeutic, researchers are exploring ways to “train” these MSCs by exposing them to specific immune signals before isolating the vesicles.
What was the purpose of this study?
In this study, the Restore Vision team at Galway explored whether EVs from MSCs that were specially “trained” using two immune-related proteins – TGF-β1 and IFN-γ – could more effectively regulate the immune system than EVs from untrained cells.
What did researchers do?
Researchers first trained human MSCs using two immune-related proteins: TGF-β1 and IFN-γ. After this training, they collected EVs released by the MSCs. These EVs were then tested in lab experiments to see how they influenced key immune cells, especially macrophages (which regulate inflammation) and T cells (which attack invaders or infected cells).
To understand why the trained EVs were more effective, researchers also used genetic analysis to understand how the MSCs changed after training and how this might explain the stronger effects of their EVs.
What did they find?
Researchers found that the trained EVs reduced inflammation more effectively than regular EVs:
- They calmed overactive immune cells
- increased anti-inflammatory molecules like Interleukin- 10 (IL-10)
- and helped produce more regulatory T cells which prevent the immune system from overreacting.Genetic analysis also revealed seven key genes that may explain why the trained EVs worked better.
What are the main implications?
These findings support the potential of using trained MSC-EVs as a safer, more efficacious cell-free way to treat immune diseases, including rare eye immune diseases – a great focus of the RESTORE VISION project. The study was done in the lab, so further pre-clinical and safety tests will be needed before these EVs can be used clinically. Still, the findings offer hope for developing better therapies to control immune responses with fewer risks.