Abstract

Extracellular Vesicles as Reprogramming Reagents for induced Tissue Regeneration (iTR)

Dana Larocca, VP Discovery Research, AgeX Therapeutics

The global demographic shift toward an older population has created an urgent unmet medical need for effective therapeutics to treat chronic diseases of aging.  Our somatic restriction model views aging as a progressive loss of robust replicative and regenerative potential, initially observed in the developing embryo, that leads to the eventual loss of tissue homeostasis associated with aging.  We are currently assessing the ability of natural and engineered EVs to restore aging adult cells to a younger more regenerative state.  Accordingly, we hypothesized that EVs from young highly regenerative embryonic progenitor cell lines could potentially act as reprogramming reagents to induce regeneration in aging adult cells and tissues.  Toward this end, we have been mining our PureStem library of over 200 highly scalable and clonally pure embryonic progenitor cell lines to identify cellular sources of EVs capable of induced Tissue Regeneration (iTR). Using angiogenesis as a model system of vascular regeneration, we identified embryonic progenitor cell lines that produce EVs capable of stimulating adult endothelial cell migration and tube formation with increased potency compared to EVs from adult cell lines.  We are using comparative transcriptomic analysis of our PureStem library to identify additional candidate cell lines that produce angiogenic EVs. In addition, we identified miRNA cargo associated with increased angiogenic activity that we are currently loading into native exosomes to determine whether they can enhance therapeutic potency. Our data indicate the potential of embryonic progenitor cell lines as a source of natural and engineered EVs for treating cardiovascular disease as well as other degenerative diseases of aging.