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

Project Summary Chronic tendon injury and tendinopathy are extremely common and painful degenerative conditions whose prevalence reachesin adults overMost of these people don t seek surgical treatmenthowever they do receive injections or physical therapy to improve pain management and regain a small amount of strengthThere are no non surgical tendinopathy therapies that are proven clinically effectivetherefore there is an urgent clinical need for the development of novel therapies for this conditionAdult stem cells are characterized by their self renewing capacity and multipotency making them attractive starting materials for tendonand ligament tissue engineering and regenerative medicine applicationsHowever stem cells do not necessarily repair tissue by differentiating into the desired tissue typebut act more in a regulatory roleThis is accomplished through paracrine effects and cell cell interactions which can be carried out via secreted extracellular vesiclesincluding exosomesIf many of the regenerative properties of stem cells can be credited to exosomesthere will be a paradigm shift in how we view regenerative medicine and therapeutics for many indicationslive cell therapies could be replaced with exosome based biologicsOur focus is to determine the feasibility of using stem cell derived exosomes that have been specifically tuned to break the ineffective repair cycle inherent in tendinopathyProteomic and genomic analysis of exosome content has revealed a broad range of signaling factors that are both cell type specific as well as differentially regulated by the secreting cellsenvironmentBased on these phenomenathis Phase I program is intended to address two hypothesesthe cargo of stem cell derived exosomes can betunedtoward pro healing factors by altering the cellsenvironment andthese pro healing exosomes can be used as a potential tendon healing regenerative therapeuticWe have developed a bioreactor based production system for manufacturing exosomes from various cell typesincluding stem cellsThe bioreactor is an ideal system to test exosome cargo tunabilityproviding a defined environment and optimized exosome purification capabilitiesThis Phaseproject is designed to provide in vitro and in vivo evidence for the further development of this therapeutic approachWe will assess the healing potential of stem cell exosomes derived from two unique tissue sources using our established tenocyte culture systemThis information will provide the basis to test the most effective exosomes in a rat tendon healing modelSuccessful results will lead to further developmentmechanistic studiesagerelated effects and in vivo efficacy assessments in other tendon healing models leading to our ultimate goal of developing an allogeneic therapy for chronic tendinopathy and acute tendon healing Project Narrative Chronic tendon injury and tendinopathy are very common and painful degenerative conditions predominantly afflicting those over the age ofBecause there are no clinically effective nonsurgical treatmentswe plan to exploit stem cell derived extracellular vesicles as a biologic derived therapyleveraging the regenerative and healing properties of adult stem cells to address this unmet clinical need