Extracellular Vesicles Secreted by TDO2-Augmented Fibroblasts Regulate Pro-inflammatory Response in Macrophages.
Publication Year:
2021
PubMed ID:
34751245
Funding Grants:
Public Summary:
Tiny bubbles released by cells, called extracellular vesicles (EVs), help cells talk to each other and can be used as therapy. Scientists found that a protein called TDO2, controlled by an important cell pathway called Wnt signaling, is key to making these EVs effective.
When they increased TDO2 in skin cells that normally don’t help much, the EVs those cells released became better at calming inflammation, especially by reducing the immune response of certain cells called macrophages.
In animal tests, these EVs helped protect the heart after injury. This study shows that TDO2 plays an important role in making cell therapies and their EVs more powerful in reducing inflammation and protecting the heart.
Scientific Abstract:
Extracellular vesicles (EVs) are secreted lipid bilayer vesicles that mediate cell to cell communication and are effectors of cell therapy. Previous work has shown that canonical Wnt signaling is necessary for cell and EV therapeutic potency. Tryptophan 2,3-dioxygenase (TDO2) is a target gene of canonical Wnt signaling. Augmenting TDO2 in therapeutically inert fibroblasts endows their EVs with immunomodulatory capacity including attenuating inflammatory signaling in macrophages. Transcriptomic analysis showed that macrophages treated with EVs from fibroblasts overexpressing TDO2 had blunted inflammatory response compared to control fibroblast EVs. In vivo, EVs from TDO2-overexpressing fibroblasts preserved cardiac function. Taken together, these results describe the role of a major canonical Wnt-target gene (TDO2) in driving the therapeutic potency of cells and their EVs.