# Exploring the Potential of Extracellular Vesicles from Atlantic Cod (Gadus morhua L.) Serum and Mucus for Wound Healing In Vitro

## TL;DR

This study explores the potential of extracellular vesicles from Atlantic cod for promoting wound healing in human and mouse cell models.

## Contribution

This is the first study to investigate the regenerative potential of extracellular vesicles from cod mucus and serum in wound healing.

## Key findings

- Cod-derived extracellular vesicles showed protective effects and accelerated wound closure in in vitro models.
- Cod serum and mucus EVs had differing capacities to influence fibroblast and keratinocyte wound healing.
- EV protein cargoes were linked to immune, stress, and wound-healing processes through enriched pathways.

## Abstract

Skin wound healing is a major research field in medicine, where improved and new therapeutic approaches are in demand. Biological agents and materials from the Atlantic cod have shown promising potential in wound treatment applications. Therefore, it is important to understand both cellular and molecular factors involved and explore further cod-derived agents. Extracellular vesicles (EVs) are small membrane vesicles released from cells and can be isolated from biofluids, such as blood and mucus. EVs are important for cell communication, and EVs from various cell types, including stem cells, have been identified as potent agents for tissue regeneration. This is the first study to assess the possible pro-regenerative effects of EVs isolated from cod mucus and serum in wound healing models of human and mouse cells. We report preliminary promising results on the protective effects of cod EVs in wound healing, with the potential to accelerate wound closure and elevate key factors involved in promoting wound healing.

Novel therapeutic approaches for wound healing have included biomaterials from the Atlantic cod (Gadus morhua L.), with promising results in wound management. The use of extracellular vesicles (EVs), which can be isolated from cod biofluids, remains to be studied. EVs play key roles in cellular communication, and their use both as biomarkers and as therapeutic agents is widely reported in human pathologies, particularly with respect to mesenchymal stem cells. This pilot study characterized the total proteomic cargo content of EVs from cod serum and mucus and assessed the EVs’ potential for regenerative activity in wound-healing processes, using human and mouse fibroblast and keratinocyte in vitro scratch injury models. The pro-regenerative potential of both cod serum EVs and mucus EVs was identified, with differing capacities for accelerating wound closure in fibroblast and keratinocyte cells. This was further supported by varying effects of the cod serum EVs and mucus EVs on cellular vimentin and FGF-2 levels. The serum EV and mucus EV protein cargoes differed with respect to abundance of protein hits and associated enriched functional GO and KEGG pathways, but both were associated with immune, stress and wound-healing processes. Cod EVs may present as innovative therapeutic options for regenerative medicine applications, and our reported findings provide valuable insights for future in-depth studies.