Defining the activity of pro-reparative extracellular vesicles in wound healing based on miRNA payloads and cell type-specific lineage mapping

Small extracellular vesicles (EVs), released by cells, carry a cargo of biologically active molecules that orchestrate the response of various cell types, particularly in the intricate process of cutaneous wound healing.

A recent study delves into the potential of EVs as therapeutic agents in the context of impaired wound healing, such as that seen in diabetic obese individuals. Using a model of cutaneous injury, researchers at the University of California San Diego explored the ability of EVs from the wound site to enhance healing in diabetic obese mice.

Intriguingly, the researchers identified specific microRNAs (miRNAs) within the EVs that seemed to boost their pro-reparative properties. One miRNA of particular interest was miR-425-5p, whose downregulation was associated with the regulation of a protein called adiponectin known for its insulin-sensitizing properties.

To trace the origin of these EVs, researchers employed a clever technique using a fluorescent reporter protein fused with a tetraspanin CD9, a marker abundant in EVs. By tracking the expression of miR-425-5p in macrophage-derived EVs and assessing macrophage abundance at EV donor sites, they mapped the release of these therapeutic messengers.

Further investigation revealed that EVs released under the control of a macrophage-specific promoter were most abundant and were efficiently taken up by dermal fibroblasts, suggesting a targeted delivery mechanism.

The study proposes a fascinating mechanism by which pro-reparative EVs shuttle miRNAs like miR-425-5p to stimulate the expression of adiponectin, ultimately aiding in wound closure. These tiny messengers foster intercellular signaling, resolving inflammation, promoting basal keratinocyte proliferation, and accelerating the healing process.

As our understanding of the intricate interplay between cells and EVs deepens, the potential for harnessing these tiny messengers as therapeutic agents in wound healing grows. With further research, EV-based therapies could offer new hope for individuals with impaired wound healing, bringing us closer to effective treatments for this challenging condition.

Park DJ, Choi W, Sayeed S, Dorschner RA, Rainaldi J, Ho K, Kezios J, Nolan JP, Mali P, Costantini T, Eliceiri BP. (2024) Defining the activity of pro-reparative extracellular vesicles in wound healing based on miRNA payloads and cell type-specific lineage mapping. Mol Ther [Epub ahead of print]. [abstract]

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