Restoration of Stressed Melanocytes Functions: Role of Keratinocytes Derived Exosomes

Exosomes, the extracellular organelles, have an important and defined role as cellular communication mediators and are explored for their therapeutic application. Few recent studies have also highlighted their involvement in vitiligo pathogenesis. However, the effect of keratinocyte-derived exosomes on stressed melanocytes, is still far from clear. Oxidative stress is one of the hallmarks of vitiligo pathogenesis that primarily affects melanocytes leading to the disruption of the epidermal-melanin unit. This study aims to determine whether supplementation with healthy keratinocyte-derived exosomes can reduce melanocyte stress induced by mitochondrial dysfunction or not. Primary human cell culture of keratinocytes and melanocytes were established. Stress was created in melanocytes through overexpressing the miR-2909 using an expression vector. Exosomes isolated from healthy keratinocytes were co-cultured with stressed melanocytes and the relative uptake of exosomes by stressed melanocytes was visualised and its effect on melanogenesis and mitochondrial functions was analysed. Previously in our studies we demonstrated that miR-2909 is involved in vitiligo pathogenesis and leads to the generation of ROS and decreased melanin synthesis inside melanocytes. Hence, in this study miR-2909-treated stressed melanocytes were used as a cellular vitiligo model to study the effect of exosomes. Results revealed that stressed melanocytes had significantly more uptake of exosomes compared to healthy melanocytes. These exosomes were able to increase melanocyte viability, and the expression of genes associated with melanogenesis. They also improved mitochondrial functions linked to melanocyte function restoration. Moreover, the uptake of fibroblast exosomes was less compared to those of keratinocytes. Our results revealed that exosomes from healthy keratinocytes have the potential to not only reduce stress, but also increase melanin functions through the mitochondrial activity of stressed melanocytes. This might open up new dimensions in exploring better therapeutics for vitiligo.