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Hyaluronic acid stimulation of stem cells for cardiac repair: a cell-free strategy for myocardial infarct.

Authors :
Seon‑Yeong Jeong
Bong‑Woo Park
Jimin Kim
Seulki Lee
Haedeun You
Joohyun Lee
Susie Lee
Jae‑Hyun Park
Jinju Kim
Woosup Sim
Kiwon Ban
Joonghoon Park
Hun‑Jun Park
Soo Kim
Source :
Journal of Nanobiotechnology; 4/4/2024, Vol. 22 Issue 1, p1-20, 20p, 9 Graphs
Publication Year :
2024

Abstract

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-β1- 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14773155
Volume :
22
Issue :
1
Database :
Complementary Index
Journal :
Journal of Nanobiotechnology
Publication Type :
Academic Journal
Accession number :
181232646
Full Text :
https://doi.org/10.1186/s12951-024-02410-x