Development of a Stem Cell-derived Cell-free Therapeutic for Stress Urinary Incontinence

Abstract Stress urinary incontinenceSUIcan result from a combinatorial neuromuscular injury to the pudendal nerve and the muscle it innervatesthe external urethral sphincterEUScompounded by the biochemical effects of agingThe mechanisms of SUI development include incomplete pudendal nerve regeneration and EUS sphincter repair from the maternal polytrauma of childbirth as well as biochemical changes with agingSurgery and injectable bulking agents are used to treat SUIbut there is currently no effective therapeutic for this indicationTheratome BioIncis developing a next generation regenerative medicine that is based on factors secreted by adult adipose derived stem cellsThis therapeuticTherahas demonstrated neurogenic activity in vitro and in vivo and functional improvement in preclinical models of ischemic brain injurystrokeneurodegenerative diseaseand limb ischemiaDue to its regenerative effects and prior observation that rat stem cell secretome has demonstrated efficacy in animal models of SUI we hypothesize that Theraor secretome product prepared by similar clinically compliant methods will be as effective as rat stem cell secretome in treating SUI in the proposed preclinical modelSuccessful completion of this project will result in selection of a candidate secretome preparation that can be rapidly progressed to clinical trials in SUI Narrative Stress Urinary IncontinenceSUIis a significant medical issue with profound social implicationsSUI prevalence increases with age and with multiple vaginal deliveries in female population due to combined effects of aging and injury to neuromuscular tissues of the urogenital tract and pelvic floorThere is currently no therapeutic that is effective in treatment SUIWe have previously demonstrated that a regenerative therapy comprised of rat stem cell secretome is efficacious in an animal model of SUIWe propose in this application to bridge from this rodent preparation to a clinically complianthuman stem cell secretome therapy for rapid translation to clinical trials