Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Sep 26, 2023; 15(9): 897-907
Published online Sep 26, 2023. doi: 10.4252/wjsc.v15.i9.897
Mechanism of adipose-derived mesenchymal stem cell exosomes in the treatment of heart failure
Lei Wang, Jin-Jin Zhang, Sha-Sha Wang, Liang Li
Lei Wang, Jin-Jin Zhang, Sha-Sha Wang, Liang Li, Department of Geriatric Medicine, Fourth Medical Center of PLA General Hospital, Beijing 100048, China
Author contributions: Wang L, Zhang JJ, and Wang SS contributed equally to this work and are co-first authors. Wang L, Zhang JJ, and Wang SS proposed the overall research goal and designed the research plan and model design, conducted statistical processing and analysis of the data, and are responsible for writing the first draft of the paper; Wang L, Zhang JJ, Wang SS, and Li L conducted feasibility analysis, review and supervision of the experiment; and are responsible for the review, revision and quality control of the paper; and all authors determined the final draft of the paper.
Institutional animal care and use committee statement: This study was approved by the Experimental Animal Ethics Committee of Fourth Medical Center of PLA General Hospital.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Liang Li, MM, Doctor, Department of Geriatric Medicine, Fourth Medical Center of PLA General Hospital, No. 51 Fucheng road, Haidian District, Beijing 100048, China.
Received: July 27, 2023
Peer-review started: July 27, 2023
First decision: August 3, 2023
Revised: August 16, 2023
Accepted: September 12, 2023
Article in press: September 12, 2023
Published online: September 26, 2023
Research background

This paper discusses the significant public health issue of heart failure (HF) and the limited efficacy of current treatment options. It explores the use of digoxin and angiotensin receptor blockers in HF treatment, with conflicting results regarding mortality reduction. The paper introduces mesenchymal stem cells (MSCs), specifically adipose-derived MSCs (ADMSCs), as a potential solution. However, storage and transportation requirements limit their clinical use. Exosomes (Exos), lipid bilayer vesicles secreted by cells, are proposed as an alternative. These Exos can be stored and transported easily and have shown potential in tissue repair, inflammation inhibition, and immune regulation. The aim of the research is to investigate the use of ADMSC Exos for treating HF.

Research motivation

The research motivation of the paper is to address the global public health issue of HF and the limitations of current treatment options. The authors aim to explore the potential of ADMSC Exos as a novel therapy for HF. By investigating the effects of these Exos on heart function, the researchers seek to provide insights into new diagnostic and treatment strategies for chronic HF.

Research objectives

The research objectives of the paper are to review the current state of diagnosis and treatment for chronic HF, explore the potential use of ADMSC Exos as a therapy, investigate the limitations of ADMSCs for clinical use, examine the functions of MSC Exos, and evaluate their effectiveness in treating HF. The ultimate goal is to contribute to the development of more effective diagnostic and treatment strategies for HF.

Research methods

The exogenous surface markers of adipose derived MSCs were found and adipose derived MSCs were cultured.

Research results

The identification of surface markers showed that the surface markers CD44 and CD29 of adipose-derived stem cells (ADSCs) were well expressed, while the surface markers CD45 and CD34 of ADSCs were negative, so the cultured cells were ADSCs. Western blotting detected the Exo surface marker protein, which expressed CD63 protein but did not express calnexin protein, indicating that ADSCs derived Exos were successfully extracted.

Research conclusions

The secretion of MSCs from adipose tissue can increase ATP level, block cardiomyocyte apoptosis, and enhance the heart function of animals susceptible to HF. The inhibition of Bax, caspase-3 and p53 protein expression may be related to this process.

Research perspectives

Current research suggests that HF is a chronic condition caused by neuroendocrine system activation, leading to ventricular remodeling and cardiomyocyte death. Preventing cardiomyocyte apoptosis is crucial in managing HF. Doxorubicin, a chemotherapy drug, can cause heart damage. ADSC Exos have shown potential in promoting heart regeneration and immune regulation. They can inhibit cardiomyocyte apoptosis, alleviate structural remodeling, and improve cardiac function. ADSC Exos may achieve these effects through the PI3K/Akt signaling pathway. Elevated levels of atrial natriuretic peptide (ANP) are associated with HF, and ADSC Exos can reduce ANP and b-type natriuretic peptide concentrations, improving cardiac function. ADSC Exos can also increase ATP content in cardiac tissue to maintain normal myocardial activity. They inhibit the expression of apoptotic proteins while promoting anti-apoptotic protein expression, thus improving cardiac function. Overall, ADSC Exos have therapeutic potential for HF, but further research is needed.