Therapeutic potential of exosomes derived from human endometrial mesenchymal stem cells for heart tissue regeneration after myocardial infarction

Myocardial infarction (MI) is the most common cardiovascular disease (CVD) and the leading cause of mortality worldwide. Recent advancements have identified human endometrial mesenchymal stem cells (hEnMSCs) as a promising candidate for heart regeneration, however, challenges associated with cell-ba...

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Main Authors: Masoumeh Sepehri, Shahram Rabbani, Jafar Ai, Naghmeh Bahrami, Hossein Ghanbari, Mojdeh Salehi Namini, Majid Sharifi, Fatemeh Kouchakzadeh, Mohsen Abedini Esfahlani, Somayeh Ebrahimi-Barough
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Regenerative Therapy
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352320425000070
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author Masoumeh Sepehri
Shahram Rabbani
Jafar Ai
Naghmeh Bahrami
Hossein Ghanbari
Mojdeh Salehi Namini
Majid Sharifi
Fatemeh Kouchakzadeh
Mohsen Abedini Esfahlani
Somayeh Ebrahimi-Barough
author_facet Masoumeh Sepehri
Shahram Rabbani
Jafar Ai
Naghmeh Bahrami
Hossein Ghanbari
Mojdeh Salehi Namini
Majid Sharifi
Fatemeh Kouchakzadeh
Mohsen Abedini Esfahlani
Somayeh Ebrahimi-Barough
author_sort Masoumeh Sepehri
collection DOAJ
description Myocardial infarction (MI) is the most common cardiovascular disease (CVD) and the leading cause of mortality worldwide. Recent advancements have identified human endometrial mesenchymal stem cells (hEnMSCs) as a promising candidate for heart regeneration, however, challenges associated with cell-based therapies have shifted focus toward cell-free treatments (CFTs), such as exosome therapy, which show considerable promise for myocardial tissue regeneration. MI was induced in male Wistar rats by occluding the left anterior descending (LAD) coronary artery. The hEnMSCs-derived exosomes (hEnMSCs-EXOs) were encapsulated in injectable fibrin gel inside the cardiac tissue. The encapsulated hEnMSC-EXOs were administered, and their effects on myocardial regeneration, angiogenesis, and heart function were monitored for 30 days post-MI. The treatments were evaluated through histological analysis, echocardiographic parameters of left ventricular internal dimension at end-diastole (LVIDD) and end-systole (LVID), left ventricular end-diastole volume (LVEDV), left ventricular end-systole volume (LVESV), and left ventricular ejection fraction (LVEF) and molecular studies. Histological findings demonstrated significant fibrosis and left ventricular remodeling following MI. Treatment with fibrin gel-encapsulated hEnMSCs-EXOs substantially reduced fibrosis, enhanced angiogenesis, and prevented heart remodeling, leading to improved cardiac function. Notably, 30 days after encapsulated hEnMSCs-EXOs were delivered corresponded with a less inflammatory microenvironment, supporting cardiomyocyte retention in ischemic tissue. This study highlights the potential of encapsulated hEnMSCs-EXOs in fibrin gel as a novel therapeutic strategy for ischemic myocardium repair post-MI. The findings underscore the importance of biomaterials in advancing stem cell-based therapies and lay a foundation for clinical applications to mitigate heart injury following MI.
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spelling doaj-art-eddaf01b965b429cb65a52371b124f002025-08-20T02:46:59ZengElsevierRegenerative Therapy2352-32042025-03-012845146110.1016/j.reth.2025.01.007Therapeutic potential of exosomes derived from human endometrial mesenchymal stem cells for heart tissue regeneration after myocardial infarctionMasoumeh Sepehri0Shahram Rabbani1Jafar Ai2Naghmeh Bahrami3Hossein Ghanbari4Mojdeh Salehi Namini5Majid Sharifi6Fatemeh Kouchakzadeh7Mohsen Abedini Esfahlani8Somayeh Ebrahimi-Barough9Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, IranResearch Center for Advanced Technologies in Cardiovascular Medicine, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, IranDepartment of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, IranDepartment of Medical Nanotechnology, School of Advanced Technologies in Medicine, University of Medical Sciences, Tehran, IranDepartment of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Tissue Engineering, School of Medicine, Shahrood University of Medical Sciences, Shahroud, IranDepartment of Histology, School of Paramedical, Shahid Sadoughi University of Medical Sciences, Yazd, IranDepartment of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Corresponding author. Department of Tissue Engineering, School of Advanced Technologies in Medicine, University of Medical Sciences, Tehran, Iran.Myocardial infarction (MI) is the most common cardiovascular disease (CVD) and the leading cause of mortality worldwide. Recent advancements have identified human endometrial mesenchymal stem cells (hEnMSCs) as a promising candidate for heart regeneration, however, challenges associated with cell-based therapies have shifted focus toward cell-free treatments (CFTs), such as exosome therapy, which show considerable promise for myocardial tissue regeneration. MI was induced in male Wistar rats by occluding the left anterior descending (LAD) coronary artery. The hEnMSCs-derived exosomes (hEnMSCs-EXOs) were encapsulated in injectable fibrin gel inside the cardiac tissue. The encapsulated hEnMSC-EXOs were administered, and their effects on myocardial regeneration, angiogenesis, and heart function were monitored for 30 days post-MI. The treatments were evaluated through histological analysis, echocardiographic parameters of left ventricular internal dimension at end-diastole (LVIDD) and end-systole (LVID), left ventricular end-diastole volume (LVEDV), left ventricular end-systole volume (LVESV), and left ventricular ejection fraction (LVEF) and molecular studies. Histological findings demonstrated significant fibrosis and left ventricular remodeling following MI. Treatment with fibrin gel-encapsulated hEnMSCs-EXOs substantially reduced fibrosis, enhanced angiogenesis, and prevented heart remodeling, leading to improved cardiac function. Notably, 30 days after encapsulated hEnMSCs-EXOs were delivered corresponded with a less inflammatory microenvironment, supporting cardiomyocyte retention in ischemic tissue. This study highlights the potential of encapsulated hEnMSCs-EXOs in fibrin gel as a novel therapeutic strategy for ischemic myocardium repair post-MI. The findings underscore the importance of biomaterials in advancing stem cell-based therapies and lay a foundation for clinical applications to mitigate heart injury following MI.http://www.sciencedirect.com/science/article/pii/S2352320425000070Human endometrium mesenchymal stem cellsMyocardial infarctionHeart regenerationExosomesAngiogenesis
spellingShingle Masoumeh Sepehri
Shahram Rabbani
Jafar Ai
Naghmeh Bahrami
Hossein Ghanbari
Mojdeh Salehi Namini
Majid Sharifi
Fatemeh Kouchakzadeh
Mohsen Abedini Esfahlani
Somayeh Ebrahimi-Barough
Therapeutic potential of exosomes derived from human endometrial mesenchymal stem cells for heart tissue regeneration after myocardial infarction
Regenerative Therapy
Human endometrium mesenchymal stem cells
Myocardial infarction
Heart regeneration
Exosomes
Angiogenesis
title Therapeutic potential of exosomes derived from human endometrial mesenchymal stem cells for heart tissue regeneration after myocardial infarction
title_full Therapeutic potential of exosomes derived from human endometrial mesenchymal stem cells for heart tissue regeneration after myocardial infarction
title_fullStr Therapeutic potential of exosomes derived from human endometrial mesenchymal stem cells for heart tissue regeneration after myocardial infarction
title_full_unstemmed Therapeutic potential of exosomes derived from human endometrial mesenchymal stem cells for heart tissue regeneration after myocardial infarction
title_short Therapeutic potential of exosomes derived from human endometrial mesenchymal stem cells for heart tissue regeneration after myocardial infarction
title_sort therapeutic potential of exosomes derived from human endometrial mesenchymal stem cells for heart tissue regeneration after myocardial infarction
topic Human endometrium mesenchymal stem cells
Myocardial infarction
Heart regeneration
Exosomes
Angiogenesis
url http://www.sciencedirect.com/science/article/pii/S2352320425000070
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