Abstract

Stem Cell Extracellular Vesicles as a Novel Therapy for Age-related Tendinopathy

John Ludlow, Executive Director, Zen Bio Inc

Aging is the principal risk factor associated with tendinopathy and also contributes to a significant decrease in the ability to efficiently heal chronic tendon injury by altering the complex and highly coordinated processes required for normal resolution. In addition to increases in lifespan and a growing aging population that is remaining active, there is a concomitant rise in the prevalence of comorbidities and tendinopathy risk factors such as obesity and diabetes. These factors have led to a very high prevalence of tendon injuries in those over 60 years of age, reaching 50% of this population, resulting in decreased quality of life and an economic burden in the billions of dollars. The use of biological and stem cell therapies for tendon healing and repair have been widely investigated and have demonstrated some potential for soft tissue regeneration. Secreted extracellular vesicles (EVs), such as exosomes, are packed with potent pro-repair proteins and RNA cargos that are both cell type-specific, as well as differentially produced and secreted according to the cellular environment. We have demonstrated that mild heat shock improves the repair activity of stem cell-derived EVs in vitro and in vivo. By manipulating the cellular environment, we have found that we can alter stem cell EV production and secretion. Our results have validated an approach of manipulating the cellular environment in a closed-system bioreactor to modify the bioactive cargo of secreted EVs for improved tendon healing. This presentation will describe the further development of our pro-healing EV therapeutic approach to treat tendon injuries and tendinopathy specifically afflicting the elderly.