Exosomes derived from cardiac telocytes exert positive effects on endothelial cells

Telocytes are novel cells that have been documented in the interstitium of multiple organs; however, their role in the heart remains unclear. This study aimed to identify cardiac telocytes by their morphological and molecular features and investigate whether their exosomes affect cardiac endothelial cells. To this end, rat cardiac telocytes were cultured and stained with methylene blue, Janus Green B, and MitoTracker green, or with antibodies for established cell surface markers, and examined by microscopy. In addition, telocyte organelles and exosome release were examined by transmission electron microscopy. To investigate exosome functions, we isolated exosomes from telocytes and co-cultured them with endothelial cells in vitro, as well as transfusing them into a rat model of myocardial infarction. We confirmed that cultured telocytes exhibit normal characteristics, including long, thin prolongations with a moniliform appearance, as well as positive expression of c-Kit, CD34, and vimentin. Furthermore, we observed mitochondria throughout the cell body and telopodes, and found that telocytes actively secrete exosomes. Interestingly, endothelial cells cultured with telocyte supernatants or exosomes exhibited increased proliferation, migration, and formation of capillary-like structures, and these effects were attenuated when exosomes were depleted from telocyte supernatants. Finally, treating myocardial infarction-induced rats with telocyte exosomes resulted in decreased cardiac fibrosis, improved cardiac function, and increased angiogenesis. Taken together, our results provide novel insight into cardiac telocytes, suggesting that they communicate with neighboring endothelial cells via exosome secretion and that these exosomes exert potentially beneficially effects.