Mesenchymal stem cell-derived extracellular vesicles as a novel therapeutic modality for brain aging

Age—related cognitive decline is a common phenotype of normal aging resulting in reduced learning abilities, decision making and executive functions. Cognitive decline can severely impair elderly people's independence, quality of life that eventually increase their dependance on caregivers. As the elderly population is increasing, age—related cognitive decline become an increasing problem. Stem cells provide a novel therapeutic approach for treating diseases. Stem cells were also found to prevent age—related cognitive decline in experimental studies. Stem cells effect is mediated by the secretion of special vesicles loaded with therapeutic substances. In the present proposal we aim to apply stem cell—derived vesicles, with anti—inflammation properties specifically designed to target brain aging. Furthermore, we aim to compare their effect with vesicles derived from aged or senescent stem cells. The significance of the present proposal stems from understanding the mechanisms by which stem cell—derived vesicles ameliorate or promote brain aging. Such understanding can be further utilized for developing novel therapies for age-related cognitive impairment. Novel therapies can be based on extracellular vesicles administration or on conventional drug therapy, based on the discovered mechanisms. Since age-related cognitive decline shares pathophysiological mechanisms (i.e. inflammation) with other disorders, our finding may have broader impact than ”normal” brain aging. Indeed, we believe that our study will also shed light on the mechanisms of neurodegenerative diseases and other age—related diseases and may lead to the discovery of new intervention strategies for age—related cognitive impairment.