Abstract
BackgroudMyocardial infarction (MI) is one of the leading causes of global death. Dendritic cell-derived exosomes (DEXs) provide us with the possibility of improving cardiac function after MI but are limited by low retention times and short-lived therapeutic effects. In this study, we developed a novel drug delivery system incorporating alginate hydrogel that continuously releases DEXs and investigated the mechanisms underlying the action of DEXs in the improvement of cardiac function after MI.ResultsWe incorporated DEXs with alginate hydrogel (DEXs-Gel) and investigated controlled released ability and rheology, and found that DEXs-Gel release DEXs in a sustainable mammer and prolonged the retention time of DEXs but had no detrimental effects on the migration in vivo. Then DEXs-Gel was applicated in the MI model mice, we found that DEXs-Gel siginificantly enhanced the therapeutic effects of DEXs with regards to improving cardiac function after MI. Flow cytometry and immunofluorescence staining revealed that DEXs significantly upregulated the infiltration of Treg cells and M2 macrophages into the border zoom after MI, and DEXs activated regulatory T (Treg) cells and shifted macrophages to reparative M2 macrophages, both in vitro and in vivo.ConclusionOur novel delivery method provides an innovative tool for enhancing the therapeutic effects of DEXs after MI. Further analysis revealed that DEXs exert effect by activating Treg cells and by modifying the polarization of macrophages.Graphic
Highlights
Worldwide, myocardial infarction (MI) is still the primary cause of cardiovascular mortality and disability [1]
We demonstrated that derived exosomes (DEXs) improved cardiac function by migrating into the lymphatic system and by activating C D4+T cells[12]; whether the gel affects the migration of DEXs and whether DEXs-Alginate hydrogel (Gel) could enhance the therapeutic effects of DEXs remain unknown
The ultrastructure of the DEXs were demonstrated by transmission electron microscopy (TEM) (Fig. 1B) and particle size distributions were determined via nanoparticle tracking analysis (NTA); the mode diameter was 106.5 nm (Fig. 1D)
Summary
Myocardial infarction (MI) is still the primary cause of cardiovascular mortality and disability [1]. Exosomes (EXs) are a type of extracellular vesicle that are secreted by cells and contain proteins, DNA, and RNA [7]. It has become increasingly clear that exosomes from various cell types engage with the immune system as messengers of intercellular communication [7,8,9]. Dendritic cell (DC)derived exosomes (DEXs) are known to participate in antigen presentation [10], immune activation, and inhibition [11]. The simple delivery of a greater number of EXs did not prolong retention times; rather, this generated a range of additional problems [15].
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