Key result
Hyaluronic acid-primed stem cell vesicles improve cardiac function and reduce adverse remodeling post-MI.
Why the study?
Myocardial infarction remains a major global burden, and it was unknown whether extracellular vesicles from hyaluronic acid-primed induced mesenchymal stem cells could enhance cardiac repair after MI.
Extracellular vesicles from hyaluronic acid-primed mesenchymal stem cells offer a promising cell-free strategy to improve cardiac repair and function after myocardial infarction.
Background Myocardial infarction (MI), a representative form of ischemic heart disease, remains a huge burden worldwide. This study aimed to explore whether extracellular vesicles (EVs) secreted from hyaluronic acid (HA)-primed induced mesenchymal stem cells (HA-iMSC-EVs) could enhance the cardiac repair after MI. Results HA-iMSC-EVs showed typical characteristics for EVs such as morphology, size, and marker proteins expression. Compared with iMSC-EVs, HA-iMSC-EVs showed enhanced tube formation and survival against oxidative stress in endothelial cells, while reduced reactive oxygen species (ROS) generation in cardiomyocytes. In THP-1 macrophages, both types of EVs markedly reduced the expression of pro-inflammatory signaling players, whereas HA-iMSC-EVs were more potent in augmenting anti-inflammatory markers. A significant decrease of inflammasome proteins was observed in HA-iMSC-EV-treated THP-1. Further, phospho-SMAD2 as well as fibrosis markers in TGF-b1-stimulated cardiomyocytes were reduced in HA-iMSC-EVs treatment. Proteomic data showed that HA-iMSC-EVs were enriched with multiple pathways including immunity, extracellular matrix organization, angiogenesis, and cell cycle. The localization of HA-iMSC-EVs in myocardium was confirmed after delivery by either intravenous or intramyocardial route, with the latter increased intensity. Echocardiography revealed that intramyocardial HA-iMSC-EVs injections improved cardiac function and reduced adverse cardiac remodeling and necrotic size in MI heart. Histologically, MI hearts receiving HA-iMSC-EVs had increased capillary density and viable myocardium, while showed reduced fibrosis. Conclusions Our results suggest that HA-iMSC-EVs improve cardiac function by augmenting vessel growth, while reducing ROS generation, inflammation, and fibrosis in MI heart.
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Jeong et al. (2023) studied Myocardial infarction. HA-iMSC-EVs vs. iMSC-EVs was evaluated on Cardiac function, adverse cardiac remodeling, and necrotic size. Intramyocardial injection of extracellular vesicles from hyaluronic acid-primed induced mesenchymal stem cells improved cardiac function and reduced adverse remodeling and necrotic size in MI hearts.
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