Siraj A, Haneef K. Role of hydrogen peroxide preconditioning in mesenchymal stem cell-mediated heart regeneration: Molecular insights. World J Cardiol 2025; 17(8): 107437 [DOI: 10.4330/wjc.v17.i8.107437]
Corresponding Author of This Article
Kanwal Haneef, PhD, Assistant Professor, Dr. Zafar H. Zaidi Center for Proteomics, University of Karachi, University Road, Karachi 75270, Sindh, Pakistan. k.haneef@uok.edu.pk
Research Domain of This Article
Cell Biology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Cardiol. Aug 26, 2025; 17(8): 107437 Published online Aug 26, 2025. doi: 10.4330/wjc.v17.i8.107437
Role of hydrogen peroxide preconditioning in mesenchymal stem cell-mediated heart regeneration: Molecular insights
Anum Siraj, Kanwal Haneef
Anum Siraj, Kanwal Haneef, Dr. Zafar H. Zaidi Center for Proteomics, University of Karachi, Karachi 75270, Sindh, Pakistan
Author contributions: Siraj A conducted the literature review and completed the first draft of the paper; Haneef K conceived the idea, provided detailed guidance, and finalized the paper; all of the authors read and approved the final version of the manuscript to be published.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kanwal Haneef, PhD, Assistant Professor, Dr. Zafar H. Zaidi Center for Proteomics, University of Karachi, University Road, Karachi 75270, Sindh, Pakistan. k.haneef@uok.edu.pk
Received: March 25, 2025 Revised: May 22, 2025 Accepted: August 1, 2025 Published online: August 26, 2025 Processing time: 149 Days and 21.1 Hours
Abstract
Mesenchymal stem cells (MSCs) possess unique properties such as immunomodulation, paracrine actions, multilineage differentiation, and self-renewal. Therefore, MSC-based cell therapy is an innovative approach to treating various degenerative illnesses, including cardiovascular diseases. However, several challenges, including low transplant survival rates, low migration to the ischemic myocardium, and poor tissue retention, restrict the application of MSCs in clinical settings. These undesirable cell therapy outcomes mainly originated due to the overproduction of reactive oxygen species (ROS) in the injured heart. MSCs' stress-coping capacity can be enhanced by preconditioning them under conditions similar to the microenvironment of wounded tissues. Hydrogen peroxide (H2O2) is a ROS that has been shown to activate protective cellular mechanisms such as survival, proliferation, migration, paracrine effects, and differentiation at sublethal doses. These processes are induced via phosphatidylinositol 3-kinase/protein kinase B, p38 mitogen-activated protein kinases, c-Jun N-terminal kinase, Janus kinase/signal transducer and activator of the transcription, Notch1, and Wnt signaling pathways. H2O2 preconditioning could lead to many clinical benefits, including ischemic injury reduction, enhanced survival of cellular transplants, and tissue regeneration. In this review, we present an overview of stem cell preconditioning methods and the biological functions activated by H2O2 preconditioning. Furthermore, this review explores the molecular mechanisms underlying the protective cellular functions stimulated under H2O2 preconditioning.
Core Tip: Hydrogen peroxide (H2O2) preconditioning is reported to increase protective mechanisms in mesenchymal stem cells and enhance their ability to regenerate in damaged hearts. However, its molecular mechanism remains under-explored. This review highlights the studies on the protective biological functions and regulatory mechanisms associated with H2O2 preconditioning in heart regeneration. Moreover, the role of the H2O2-activated redox-sensitive transcription factors and their associated pathways in cell survival, proliferation, migration, paracrine effect, and cardiac differentiation is discussed. The molecular insights provided in this review will possibly help in the development of cardiovascular regenerative therapy.
