Abstract

Induced Tissue Regeneration (iTR) Using Extracellular Vesicles

Dana Larocca, VP Discovery Research, AgeX Therapeutics

There is a critical unmet medical need for new therapies to treat age-related diseases given the increasing burden of a global demographic shift toward older populations.  Extracellular vesicles (EVs) have been demonstrated to be largely responsible for the regenerative effects of stem cells in a variety of animal models of age-associated diseases including cardiovascular diseases.  We hypothesize that EVs made by cells from early human development will convey strong regenerative signals because this is when regenerative capacity is at its peak. We used partial differentiation of human pluripotent stem cells to derive a large library of highly scalable and clonally pure embryonic progenitor cell lines.  Over 200 progenitor lines were originally established to meet the high demands of cell purity and scalability needed to treat a large aging population.  We are now mining this diverse library of cell lines for their ability to provide a scalable source of highly regenerative EVs.  We found that embryonic progenitor derived EVs had higher angiogenic activity than adult stem cell derived EVs. Moreover, angiogenic activity was maintained by EVs produced by cells at up to at least 52 population doublings and following bioreactor scale-up.  We are currently mapping bioactivity and cargo of EVs derived from a variety of embryonic cell types including endothelial, pericyte, smooth muscle, osteochondral and brown adipocyte progenitors.  We anticipate that the resulting library of diverse embryonic EVs will be a valuable resource for developing EV therapies for cardiovascular and other age-related diseases.