Extracellular Vesicles Derived from Opuntia ficus-indica Fruit (OFI-EVs) Speed Up the Normal Wound Healing Processes by Modulating Cellular Responses

Plant-derived extracellular vesicles (EVs) have been recognized as important mediators of intercellular communication able to transfer active biomolecules across the plant and animal kingdoms. EVs have demonstrated an impressive array of biological activities, displaying preventive and therapeutic potential in mitigating various pathological processes. Indeed, the simplicity of delivering exogenous and endogenous bioactive molecules to mammalian cells with their low cytotoxicity makes EVs suitable agents for new therapeutic strategies for a variety of pathologies. In this study, EVs were isolated from Opuntia ficus-indica fruit (OFI-EVs) and characterized by particle size distribution, concentration, and bioactive molecule composition. OFI-EVs had no obvious toxicity and demonstrated a protective role in the inflammatory process and oxidative stress in vitro model of chronic skin wounds. The results demonstrated that pretreatment with OFI-EVs decreased the activity and gene expression of pro-inflammatory cytokines (IL-6, IL-8, and TNF-α) in the LPS-stimulated human leukemia monocytic cell line (THP-1). Furthermore, OFI-EVs promote the migration of human dermal fibroblasts (HDFs), speeding up the normal wound healing processes. This study sheds light, for the first time, on the role of OFI-EVs in modulating important biological processes such as inflammation and oxidation, thereby identifying EVs as potential candidates for healing chronic cutaneous wounds.