한빛사논문
- 조회267
Seon‑Yeong Jeong1†, Bong‑Woo Park2,3†, Jimin Kim1, Seulki Lee1, Haedeun You1, Joohyun Lee1, Susie Lee2, Jae‑Hyun Park2, Jinju Kim2, Woosup Sim2, Kiwon Ban4, Joonghoon Park5, Hun‑Jun Park2,6* and Soo Kim1*
1Brexogen Research Center, Brexogen Inc., Songpa‑gu, Seoul 05855, South Korea.
2Department of Biomedicine & Health Sciences, The Catholic University of Korea, 222 Banpo‑daero, Seoho‑gu, Seoul 06591, Republic of Korea.
3Cathoic High‑Performance Cell Therapy Center and Department of Medical Life Science, College of Medicine, The Catholic University of Korea, 222 Banpo‑daero, Seoho‑gu, Seoul 06591, Republic of Korea.
4Department of Biomedical Science, City University of Hong Kong, Kowloon Tong, Hong Kong.
5Graduate School of International Agricultural Technology, Institutes of Green‑Bio Science and Technology, Seoul National University, Pyeongchang, Gangwon‑do 25354, South Korea.
6Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea, 222 Banpo‑daero, Seocho‑gu, Seoul 06591, Republic of Korea.
†Seon-Yeong Jeong and Bong-Woo Park are contributed equally.
*Correspondence: Hun‑Jun Park, Soo Kim
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.
논문정보
- Research article
- 2024년 04월 (BRIC 등록일 2024-05-09)
- 국내 연구진
- 의약학 > 응용의학
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