Evaluation of the effect of citrus sinensis derived exosomes on neurogenic differentiation of periodontal ligament stem cells

The nervous system is often irreversibly damaged by both genetic and acquired diseases throughout life. Nowadays it is determined that in a vast majority of neurodegenerative diseases, completion of tissue regeneration are extremely challenging. As a consequence, not only the differentiation of neuronal stem cells in certain regions of the brain to mature neurons but also the differentiation of adult stem cells with multipotent characteristics to functional and healthy nerve cells at various developmental stages have a considerable potential to be used in future therapies. On the other hand, in the tissues that are involved in neurons, the vesicular structures, which are about 100 nanometers in size, undertake the role of a messenger in the provision of intercellular communication. Moreover, studies have shown that exosomes have a significant effect on cellular mechanisms. However, there are no studies on the effect of plant-derived exosomes on the differentiation of adult stem cells into mature neurons. As a result, the differentiation of periodontal ligament stem cells to mature neurons and an investigation of the possible effects of Citrus sinensis derived exosomes (CSDE) on the model are aimed. Accordingly, the cells were differentiated for 10 days by utilizing multi-stage inductive media. At the end of the differentiation protocol, differentiation success and efficiency were analyzed by various experiments in terms of both morphological and transcriptional-translational characteristics. As a result of the experiments, it was determined that the induction protocol used successfully differentiated the periodontal ligament stem cells into mature neurons and CSDE increased the cell viability during the differentiation process. Accordingly, a new induction protocol that can be used for the differentiation of stem cells into neurons has emerged and it is observed that plant-derived exosomes have a positive role in the differentiation process for the first time. In the future, it is extremely important to use the designed differentiation protocol in the modeling of neuronal diseases and to investigate the effects of plant-derived exosomes in these diseases.