ABSTRACT
Despite diagnostic and therapeutic advances, cardiometabolic disease remains the leading cause of death worldwide. Extracellular vesicles (EVs), which include exosomes and microvesicles, have gained particular interest because of their role in metabolic homeostasis and cardiovascular physiology. Indeed, EVs are recognized as critical mediators of intercellular communication in the cardiovascular system. Exosomes are naturally occurring nanocarriers that transfer biological information in the setting of metabolic abnormalities and cardiac dysfunction. The study of these EVs can increase our knowledge on the pathophysiological mechanisms of metabolic disorders and their cardiovascular complications. Because of their inherent properties and composition, exosomes have been proposed as diagnostic and prognostic biomarkers and therapeutics for specific targeting and drug delivery. Emerging fields of study explore the use exosomes as tools for gene therapy and as a cell-free alternative for regenerative medicine. Furthermore, innovative biomaterials can incorporate exosomes to enhance tissue regeneration and engineering. In this work, we summarize the most recent knowledge on the role of exosomes in cardiometabolic pathophysiology while highlighting their potential therapeutic applications.
ABSTRACT
Exosomes are extracellular nanovesicles between 30 and 150 nm that serve as essential messengers for different biological signaling and pathological processes. After their discovery, a wide range of applications have been developed, especially in therapeutic drug delivery. In this context, the aim of this work was to test the efficiency of exosome-mediated human insulin delivery using exosomes extracted from three different cell lines: hepatocellular carcinoma (HepG2); primary dermal fibroblasts (HDFa) and pancreatic ß cells (RIN-m); all are related to the production and/or the ability to sense insulin and to consequently regulate glucose levels in the extracellular medium. The obtained results revealed that the optimal insulin loading efficiency was achieved by a 200 V electroporation, in comparison with incubation at room temperature. Moreover, the maximum in vitro exosome uptake was reached after incubation for 6 h, which slightly decreased 24 h after adding the exosomes. Glucose quantification assays revealed that exosome-mediated incorporation of insulin presented significant differences in HDFa and HepG2 cells, enhancing the transport in HDFa, in comparison with free human insulin effects in the regulation of extracellular glucose levels. No significant differences were found between the treatments in RIN-m cells. Hence, the results suggest that exosomes could potentially become a valuable tool for stable and biocompatible insulin delivery in diabetes mellitus treatment alternatives.