Razzaq SS, Khan I, Naeem N, Salim A, Begum S, Haneef K. Overexpression of GATA binding protein 4 and myocyte enhancer factor 2C induces differentiation of mesenchymal stem cells into cardiac-like cells. World J Stem Cells 2022; 14(9): 700-713 [PMID: 36188117 DOI: 10.4252/wjsc.v14.i9.700]
Corresponding Author of This Article
Kanwal Haneef, PhD, Assistant Professor, Dr. Zafar H. Zaidi Center for Proteomics, University of Karachi, University Road, Karachi 75270, Pakistan. k.haneef@uok.edu.pk
Research Domain of This Article
Cell Biology
Article-Type of This Article
Basic Study
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/
Syeda Saima Razzaq, Kanwal Haneef, Dr. Zafar H. Zaidi Center for Proteomics, University of Karachi, Karachi 75270, Pakistan
Irfan Khan, Asmat Salim, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Nadia Naeem, Dow Research Institute of Biotechnology & Biomedical Sciences (DRIBBS), Dow University of Health Sciences (DUHS), Ojha Campus, Karachi 75200, Pakistan
Sumreen Begum, Stem Cells Research Laboratory (SCRL), Sindh Institute of Urology and Transplantation (SIUT), Karachi 74200, Pakistan
Author contributions: Razzaq SS performed the experiments, did data analysis, and wrote the first draft of the manuscript; Khan I co-supervised the research study and assisted in transfection studies; Naeem N assisted in qPCR; Begum S assisted in immunocytochemistry; Salim A assisted in all in vitro studies; Haneef K conceived the idea, supervised the research study, and finalized the manuscript.
Supported bythe Higher Education Commission (HEC), Pakistan Scholarship for Ph.D. Studies to Razzaq SS, No. 520-148390-2BS6-011.
Institutional review board statement: The study was reviewed and approved by the institutional bioethical committee of University of Karachi (No. ICB KU-92/2020).
Conflict-of-interest statement: The authors confirm that this article has no conflict of interest to report.
Data sharing statement: No additional data are available.
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, Pakistan. k.haneef@uok.edu.pk
Received: March 28, 2022 Peer-review started: March 28, 2022 First decision: June 11, 2022 Revised: June 20, 2022 Accepted: August 30, 2022 Article in press: August 30, 2022 Published online: September 26, 2022
Abstract
BACKGROUND
Heart diseases are the primary cause of death all over the world. Following myocardial infarction, billions of cells die, resulting in a huge loss of cardiac function. Stem cell-based therapies have appeared as a new area to support heart regeneration. The transcription factors GATA binding protein 4 (GATA-4) and myocyte enhancer factor 2C (MEF2C) are considered prominent factors in the development of the cardiovascular system.
AIM
To explore the potential of GATA-4 and MEF2C for the cardiac differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs).
METHODS
hUC-MSCs were characterized morphologically and immunologically by the presence of specific markers of MSCs via immunocytochemistry and flow cytometry, and by their potential to differentiate into osteocytes and adipocytes. hUC-MSCs were transfected with GATA-4, MEF2C, and their combination to direct the differentiation. Cardiac differentiation was confirmed by semiquantitative real-time polymerase chain reaction and immunocytochemistry.
RESULTS
hUC-MSCs expressed specific cell surface markers CD105, CD90, CD44, and vimentin but lack the expression of CD45. The transcription factors GATA-4 and MEF2C, and their combination induced differentiation in hUC-MSCs with significant expression of cardiac genes i.e., GATA-4, MEF2C, NK2 homeobox 5 (NKX2.5), MHC, and connexin-43, and cardiac proteins GATA-4, NKX2.5, cardiac troponin T, and connexin-43.
CONCLUSION
Transfection with GATA-4, MEF2C, and their combination effectively induces cardiac differentiation in hUC-MSCs. These genetically modified MSCs could be a promising treatment option for heart diseases in the future.
Core Tip: Transcription factors have great potential to direct cell fate decisions during embryonic development. In this study, we investigated the overexpression of cardiac transcription factors in human umbilical cord mesenchymal stem cells to enhance their differentiation into cardiac-like cells. The synergistic effect of GATA binding protein 4 and myocyte enhancer factor 2C transcription factors increased the expression of cardiac genes and proteins. The results of this study will aid in the development of new therapeutic strategies aimed at curing heart diseases.
