Serpin-loaded extracellular vesicles promote tissue repair in a mouse model of impaired wound healing

Chronic metabolic diseases such as diabetes are characterized by delayed wound healing and a dysregulation of the inflammatory phase of wound repair. This study focuses on changes in the payload of extracellular vesicles (EVs) communicating between immune cells and stromal cells in the wound bed, which regulate the rate of wound closure.

Researchers from the University of California, San Diego used adoptive transfer of EVs from genetically defined mouse models to demonstrate a functional and molecular basis for differences in the pro-reparative biological activity of diabetic (db/db) vs. wildtype EVs in wound healing. The researchers identify several members of the Serpin family of serine protease inhibitors that are absent in db/db EVs, then they overexpress Serpin A1, F2 and G1 in EVs to evaluate their effect on wound healing in db/db mice. Serpins have an important role in regulating levels of elastase, plasmin and complement factors that coordinate immune cell signaling in full thickness wounds in a diabetic model.

The researchers establish a novel therapeutic approach by engineering the payload of EVs based on proteomic analysis. Serpin-loaded EVs were used to rescue the Serpin deficiency identified by proteomics and promote wound healing in db/db mice, as well as evaluated how EVs affected extracellular matrix remodeling and the resolution of tissue injury. Therefore, they propose that the identification of EV payloads that are downregulated in diabetic wounds can be systematically analyzed for their functional activity and potential as a therapeutic, based on whether their re-expression in engineered EVs restores normal kinetics of tissue repair in chronic wounds.

Park DJ, Duggan E, Ho K, Dorschner RA, Dobke M, Nolan JP, Eliceiri BP. (2022) Serpin-loaded extracellular vesicles promote tissue repair in a mouse model of impaired wound healing. J Nanobiotechnology 20(1):474. [article]

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