Development of a targeted cardiomyocyte delivery system utilizing cardiosphere-derived cell exosomes
Mentkowski, Kyle Indiana Robert
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Cardiovascular disease continues to be the leading cause of mortality and morbidity in the United States. Current treatment options are aimed at preventing additional injury and helping the heart work more efficiently, but are limited in their regenerative capacity. Recently, research has shown that treating the heart with various stem cell populations, including cardiosphere-derived cells (CDCs), post myocardial infarction (MI) stimulates regeneration, angiogenesis, and functional improvement. While this treatment has shown promise in early stage clinical trials, there remains a gap in the ability to efficiently deliver tissue-specific agents directly to the heart while avoiding nonspecific delivery to other organs. To fully realize the therapeutic potential of efficient delivery to the heart, we engineered CDC-derived exosomes (nano-vesicles that transport RNA and protein between cells) to express Lamp-2b, an exosomal trans-membrane protein, fused with a cardiomyocyte-specific peptide. Preliminary experiments showed enhanced exosome uptake by cardiomyocytes in vitro, establishing a novel tool for targeted delivery of anti-apoptotic drug and gene therapy.