Platelet membrane and stem cell exosome hybrids enhance cellular uptake and targeting to heart injury

Exosomes from mesenchymal stem cells have been widely studied as therapeutics to treat myocardial infarction. However, exosomes injected for therapeutic purposes face a number of challenges, including competition from endogenous exosomes, and the internalization/clearance by the mononuclear phagocyte system. There is also a lack of targeting. In this study, we hybridized stem cell-derived exosomes with platelet membranes to enhance their ability to target the injured heart and to reduce uptake by macrophages. Furthermore, we found that hybridization with platelet membranes induces macropinocytosis, enhancing the cellular uptake of exosomes by endothelial cells and cardiomyocytes drastically. In vivo studies showed the cardiac targeting ability of hybrid exosomes in a mouse model of myocardial infarction injury. Lastly, we determined cardiac functions and performed immunohistochemistry to confirm an enahnced therapeutic potency of platelet membrane modified exosomes as compared to non-modified exosomes. Our studies provide proof-of-concept data and a universal approach to enhance the binding and accumulation of exosomes in injured tissues. (c) 2021 Elsevier Ltd. All rights reserved.

Automated summary

In this study, stem cell-derived exosomes were hybridized with platelet membranes to enhance their targeting ability for injured hearts and reduce uptake by macrophages. The hybridization induced macropinocytosis, significantly increasing cellular uptake by endothelial cells and cardiomyocytes. In vivo studies demonstrated the cardiac targeting ability of these hybrid exosomes in a mouse model of myocardial infarction, suggesting a potential therapeutic benefit over non-modified exosomes.