Abstract 19186: Role of Exosomes and Their microRNA Constituents in Mediating the Therapeutic Benefits of Human Cardiosphere-Derived Cells in vitro and in Mice With Myocardial Infarction

TL;DRAbstract

Background: Exosomes are nano-sized bilayer vesicles that are secreted by most cell types. Exosomes are rich in microRNAs (mirs) which may function in a paracrine fashion. Cardiosphere-derived cells (CDCs) have been shown to regenerate heart after myocardial infarction (MI) in animal models and in the CADUCEUS clinical trial. However, most of the regenerated muscle is of innate origin, which suggests that CDCs function mainly through indirect pathways. Methods and Results: In vitro and in vivo, we compared three treatment groups: vehicle only (control), CDC-derived exosomes and normal human dermal fibroblast (NHDF)-derived exosomes. Neonatal rat cardiomyocytes (NRCMs) incubated with CDC exosomes were more frequently positive for Ki67 (n=4, p<0.001), and less frequently tunel-positive, compared to NHDF exosomes or control (n=4, p<0.01). CDC exosomes also stimulated tube formation in HUVEC cells compared to NHDF exosomes or control (p<0.05). SCID mice injected with exosomes from

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