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

Seon-Yeong Jeong; Bong-Woo Park; Jinju 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

doi:10.1186/s12951-024-02410-x

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

Seon-Yeong Jeong (Co-first Author)
, Bong-Woo Park (Co-first Author)
, Jinju 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^*

^*Corresponding author for this work

Department of Biomedical Sciences

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

16 Citations (Scopus)

46 Downloads (CityUHK Scholars)

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.

© The Author(s) 2024

Original language	English
Article number	149
Journal	Journal of Nanobiotechnology
Volume	22
Online published	4 Apr 2024
DOIs	https://doi.org/10.1186/s12951-024-02410-x
Publication status	Published - 2024

Bibliographical note

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

Humans
Hyaluronic Acid/pharmacology
Endothelial Cells/metabolism
Reactive Oxygen Species/metabolism
Proteomics
Myocardial Infarction/therapy
Myocytes, Cardiac/metabolism
Mesenchymal Stem Cells/metabolism
Fibrosis

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This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

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@article{ab8b255c9c7247ac80773e88038fb28b,

title = "Hyaluronic acid stimulation of stem cells for cardiac repair: a cell-free strategy for myocardial infarct",

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. {\textcopyright} The Author(s) 2024 ",

keywords = "Humans, Hyaluronic Acid/pharmacology, Endothelial Cells/metabolism, Reactive Oxygen Species/metabolism, Proteomics, Myocardial Infarction/therapy, Myocytes, Cardiac/metabolism, Mesenchymal Stem Cells/metabolism, Fibrosis",

author = "Seon-Yeong Jeong and Bong-Woo Park and Jinju Kim and Seulki Lee and Haedeun You and Joohyun Lee and Susie Lee and Jae-Hyun Park and Jinju Kim and Woosup Sim and Kiwon Ban and Joonghoon Park and Hun-Jun Park and Soo Kim",

note = "{\textcopyright} 2024. The Author(s).",

year = "2024",

doi = "10.1186/s12951-024-02410-x",

language = "English",

volume = "22",

journal = "Journal of Nanobiotechnology",

issn = "1477-3155",

publisher = "BioMed Central Ltd.",

}

TY - JOUR

T1 - Hyaluronic acid stimulation of stem cells for cardiac repair

T2 - a cell-free strategy for myocardial infarct

AU - Jeong, Seon-Yeong

AU - Park, Bong-Woo

AU - Kim, Jinju

AU - Lee, Seulki

AU - You, Haedeun

AU - Lee, Joohyun

AU - Lee, Susie

AU - Park, Jae-Hyun

AU - Kim, Jinju

AU - Sim, Woosup

AU - Ban, Kiwon

AU - Park, Joonghoon

AU - Park, Hun-Jun

AU - Kim, Soo

PY - 2024

Y1 - 2024

N2 - 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. © The Author(s) 2024

AB - 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. © The Author(s) 2024

KW - Humans

KW - Hyaluronic Acid/pharmacology

KW - Endothelial Cells/metabolism

KW - Reactive Oxygen Species/metabolism

KW - Proteomics

KW - Myocardial Infarction/therapy

KW - Myocytes, Cardiac/metabolism

KW - Mesenchymal Stem Cells/metabolism

KW - Fibrosis

UR - https://www.scopus.com/pages/publications/85189470771

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85189470771&origin=recordpage

U2 - 10.1186/s12951-024-02410-x

DO - 10.1186/s12951-024-02410-x

M3 - RGC 21 - Publication in refereed journal

C2 - 38570846

SN - 1477-3155

VL - 22

JO - Journal of Nanobiotechnology

JF - Journal of Nanobiotechnology

M1 - 149

ER -

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

Abstract

Bibliographical note

UN SDGs

Research Keywords

Publisher's Copyright Statement

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