Osomes and exosoms) by Izon system, revealed the presence of vesicles in typical size about 200 nm. The vesicular morphology was confirmed by atomic force microscopy, although the protein markers had been assessed accordingly to ISEV suggestions by western blotting. High-sensitivity flow cytometry (Apogee Flow program) confirmed the presence of various MSCspecific markers on MSC-EVs including receptors and adhesions. We also found MSC-EVs to be enriched in mRNAs, miRNAs and severalThursday May perhaps 18,1 CIC bioGUNE; 2Universidad Complutense Madrid, Madrid, Spain; 3CIC bioGUNE-Liverpool University, Liverpool, United Kingdomproteins from donor MSC cells as shown by real-time RT-PCR and mass spectroscopy, respectively. We found MSC-MVs to carry a number of transcripts regulating SC cardiac and angiogenic differentiation capacity. Importantly, our information (i) indicated a terrific influence of MSC-EVs on proangiogenic capacity of heart endothelial cells in vitro also as (ii) confirmed their regenerative prospective in vivo by showing improved heart histology, anatomy and function in murine AMI model. The raise in quantity of new capillaries within the spot of EV injection, could recommend the enhanced perfusion as among the main mechanisms involved within the MSC-EV EGFR Antagonist custom synthesis regeneration capacity in vivo. In summary, our data demonstrated that MSC-derived EVs represent natural nanocarriers transferring bioactive content material to mature target cells and playing an efficient role in heart regeneration in vivo. We conclude that MSC-EVs may possibly represent novel protected therapeutic tool in heart tissue regeneration, option or supporting to whole cell-based therapy in heart repair.PT03.Biodistribution and efficacy of extracellular vesicles from cardiosphere-derived cells Jennifer L. Johnson1, Ahmed Ibrahim1, Chris Sakoda1, Kenny Gouin2, Kiel Peck1, Liang Li1, Travis Antes3, Houman Hemmati1, Rachel Smith1, Linda Marban1 and Luis Rodriguez-BorladoCapricor Therapeutics; 2Cedars Sinai, CA, USA; 3Cedars-Sinai Healthcare Centre, Heart Institute, CA, USAIntroduction: Extracellular vesicles developed by cardiosphere-derived cells (CDC-EVs) happen to be shown to recapitulate the therapeutic activity of parent cells in heart-related illnesses. The capacity of CDC-EVs to cut down inflammation, attenuate fibrosis, and activate regeneration make them quite eye-catching for inflammatory illnesses remedy. Capricor is evaluating the usage of CDC-EVs for the remedy of ocular graft versus host disease (oGVHD), an indication where the solution is usually locally delivered. No preceding studies happen to be published analysing EVs biodistribution right after eye delivery. Here, we show in vivo biodistribution of CDC-EVs in an ocular alkali burn mouse model after subconjunctival or topical delivery, working with a novel qPCR-based system. We also analysed the therapeutic potential of CDC-EVs in mouse and rabbit models. Finally, CDC-EVs uptake by different cellular sorts was analysed in vitro to determine CDC-EVs target cells. Approaches: Unmodified human CDC-EVs had been injected in to the subconjunctival space or administered topically to wholesome or injured mouse eyes. In vitro uptake of dye-labelled EVs was measured by detecting intracellular fluorescence in treated cells by flow cytometry. In vivo biodistribution tracking was then performed employing a sensitive qPCR system tracking a YRNA fragment DNA-PK Source abundant in CDC-EVs. Therapeutic activity of CDC-EVs was evaluated in a rat model of corneal alkali burn injury plus a rabbit model of Sjgren’s syndrome. Outcome.
