Tuned stem cell extracellular vesicles as a novel chronic wound therapeutic

Project Summary The elderly population is rapidly increasing worldwide and those over years old are expected to comprise of the total population by These demographic changes will focus healthcare needs on those conditions more prevalent in the elderly Chronic wounds such as venous leg ulcers pressure ulcers and diabetic ulcers are over represented in the elderly population and even now present a significant healthcare burden These conditions impact approximately million patients annually with a cost to the health care system of over $ B Rarely occurring in the young the healing of these chronic wounds is confounded by age related factors such as reduced blood flow dermal atrophy increased inflammation and reduced growth factor responses The high recurrence rate and failure to respond to current therapies indicates the need for improved regenerative therapeutics that can overcome many of the age associated defects in the wound healing process Stem cell therapies represent a compelling means of tissue repair and have demonstrated wound healing and soft tissue regeneration in animal models However the intuitive concept that therapeutic stem cells engraft and differentiate at sites of tissue damage is not well supported given the low numbers of cells retained over time at application sites in vivo This suggests that their mechanisms of action occur through paracrine modalities such as secretion of bioactive vesicles including exosomes Hence exploiting stem cell derived exosomes as a biologic derived therapy rather than delivering transient stem cells to treat chronic wounds is an enticing approach 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 Based on our compelling preliminary data this Phase I proof of concept study will demonstrate that critical ex vivo environmental cues can tune stem cell derived EVs to be pro healing and that pro healing EVs are a valid chronic wound therapeutic We will achieve these goals by the following Aims manipulate the bioreactor environment to generate differential extracellular vesicle packaging in vitro testing of EV mediated regenerative activities in fibroblasts keratinocytes and endothelial cells and in vivo testing of pro healing EVs in chronic wound healing models This Phase I research program is designed to provide critical proof of concept data demonstrating manufacturing conditions and wound healing properties of stem cell derived extracellular vesicles This potential therapeutic has the unique advantage of harnessing the power of stem cells without the need for utilizing complex cell therapies in vivo Project Narrative The elderly are most likely to suffer debilitating and chronic non healing wounds Current therapies are largely ineffective and do not address the complex age related alterations in the healing process We plan to exploit stem cell derived extracellular vesicles as a biologic derived therapy leveraging the multifaceted healing properties of stem cells to address this urgent clinical need