Exploring in vitro markers of potency of extracellular vesicles from cardiosphere-derived cells in the treatment of cardiac ageing

Abstract Background Cardiac ageing is associated to heart failure with preserved ejection fraction (HF-pEF) and increased senescence, hypertrophy diastolic dysfunction. No treatments have yet proved reduce HF-pEF morbidity mortality. Cardiosphere-derived cells (CDCs) their secreted extracellular vesicles (CDC-EVs) demonstrated efficacy in old animals cardiac dysfunction, but variability of effect lack adequate potency tests remain as challenges. Purpose To explore vitro predictors protective CDC-EVs, focusing on the chronological age CDC-donors, CDC-senescence, anti-senescent pro-angiogenic effect. Methods CDCs derived from 34 patients (age range 0–81 years old, both sexes) were characterized terms proliferative migration capacities, VEGF secretion, expression specific surface markers cardiosphere size. CDC-EVs purified potential (at genetic, secretory cellular level over stromal cells) (ability induce tube formation endothelial quantified. According performance each these tests, was scored classified potent (P-EVs) non-potent (NP-EVs). The P-EVs NP-EVs then tested vivo rats induced aging. SD-rats received 3-months daily intraperitoneal injections (IP) saline (healthy control) or D-galactose. Rats D-Gal group randomly allocated receive IP (sham control, n=12), (n=7) (n=6) followed-up for one month. Results Chronological donor did not relate most CDC properties nor potency. senescence other bioactive properties, this insufficient predict CDC-EV anti-senescence In vivo, EV P-EVs, NP-EVs, prevented D-gal (2.4 vs. 2.9 mg/gr, p=0.05). This finding parallel levels galactosidase-beta 1 tissue, which sham (1.22 0.73, p=0.03) significantly different (0.86, p=0.1). tended TGFB1 expression, while fibrosis reduced perfusion. At systemic level, improved glucose metabolism drive total antioxidant capacity hair growth a healthier profile, improve any explored parameters capacity. Conclusions After further validation, matrix assay proposed here, scoring could be used suitability an allogenic product treatment ageing. Funding Acknowledgement Type funding sources: Public Institution(s). Main source(s): Instituto de Salud Carlos III, Ministerio Ciencia e Innovaciόn, Spain: PI16/01123; PI19/00161; Red Terapia Celular, Tercel, (RD16.0011.0029) CIBERCV (CB16.11.00292)