Role of ananas comosus derived exosomes in scarless cutaneous wound repair

Wound healing is a complex and dynamic process involving a great number of cellular interactions based on growth factors, cytokine, and chemokine release. Although many new therapeutic agents are being introduced to the market for their remarkable wound healing capabilities, the problem of why some organisms heal perfectly while others heal with a pathological connective tissue known as a scar remains a mystery. Scar formation is a natural process that occurs after the healing process due to dysfunctionalities in the remodeling phase that may occur either in the epithelial epidermis or the dermis. Reducing scar formation is lately gaining interest as a new area of scientific research. Following the discovery of scarless healing of the fetal skin, an explosive number of studies have highlighted striking differences between fetal and adult human skin in terms of the differences in their extracellular matrix, growth factor, and cytokine characteristics. Despite of the accumulating evidence to mitigate the scar formation, gain or loss of function of no single pathway or cell type has been shown to be responsible for scar formation therefore mimicking the scarless healing remains as a challenging issue. Nonetheless, findings from recent studies have shed light to certain aspects of scarless healing. In this respect, the use of plant-based products in the treatment medical conditions is becoming a matter of preference due to their lower side effects. Taking a parallel approach, this study aimed to evaluate the potential of scar reducing effects of Ananas comosus derived exosomes by determining their proliferative, migratory, and angiogenetic activities on the gene and protein expression levels of key factors of wound healing. Our results indicate that these exosomes activate ERK/MAPK and PI3K/AKT pathways and induce cellular proliferation and migration while increasing the ratio of transforming growth factor-β3 (TGF-β3) to TGF-β1, and certain MMPs, which is an indication for suppression of scar formation. Additionally, it has been shown that these exosomes also promote extracellular matrix reconstruction. Based on these results A. comosus exosomes emerge as a promising agent that facilitate cutaneous wound healing suppressing formation of scars.