Abstract 11898: Bovine Milk-Derived Extracellular Vesicles as a Novel Injury-Targeting Drug Delivery System Following Cardiac Injury

• Published in: Circulation (New York, N.Y.) N.Y.), 2022-11, Vol.146 (Suppl_1), p.A11898-A11898
• Main Authors: Marsh, Spencer R, Jourdan, Jane, Gourdie, Robert G
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.146.suppl_1.11898

IntroductionA novel protocol provides large amounts of highly purified small extracellular vesicles (also called exosomes) from bovine milk (Marsh et al, PMID34367882). We sought to examine the targeting potential of these pure, highly concentrated bovine milk-derived extracellular vesicles (mEVs) to injured cells and tissues, with the intent of identifying an effective drug delivery platform capable of targeting injured cardiac tissue. MethodsTargeting of mEVs to injured cells and tissues was tested in vitro using a scratch assay on human dermal fibroblast (hDFs) and MDCK cell monolayers, and in vivo, using mouse models of skin wounding and cardiac injury - methods we have previously reported (PMID:34246197; PMID:29351451). mEVs were isolated using our published approach (PMID34367882), then fluorescently tagged with Cell Tracker Deep Red (CTDR). Labelled mEVs were then applied to cell cultures at 20 ug/mL for 15 minutes post wound; cells were then rinsed, fixed and stained for cell nuclei with Hoechst. Mice were provided 2 ug/kg loaded mEV’s by oral gavage before skin surgery and induction of cardiac ischemic reperfusion injury. Mice were sacrificed 4 hours post-surgery, fixed by perfusion with 4% paraformaldehyde followed by PBS rinsing, then organs were explanted. Organs were then embedded in O.C.T, sectioned on a cryostat, and stained for nuclei and actin with FITC-Phalloidin. Imaging was performed on a Leica SP8 laser scanning confocal microscope and quantified using mEV uptake normalized to cell nuclei on ImageJ. ResultsmEV uptake was significantly increased in scratch wounded cultures of both hDFs and MDCK cells (p