Basic Study
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World J Stem Cells. Sep 26, 2022; 14(9): 700-713
Published online Sep 26, 2022. doi: 10.4252/wjsc.v14.i9.700
Overexpression of GATA binding protein 4 and myocyte enhancer factor 2C induces differentiation of mesenchymal stem cells into cardiac-like cells
Syeda Saima Razzaq, Irfan Khan, Nadia Naeem, Asmat Salim, Sumreen Begum, Kanwal Haneef
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 by the 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
ARTICLE HIGHLIGHTS
Research background

Myocardial infarction is the leading cause of death worldwide. Following myocardial infarction, billions of cardiomyocytes die, resulting in a significant loss in cardiac function. Cell-based therapies have emerged as a new area to support heart regeneration. GATA binding protein 4 (GATA-4) and myocyte enhancer factor 2C (MEF2C) are considered important transcription factors in the formation of cardiac cells during the embryonic development.

Research motivation

Stem cell based therapies are considered a promising approach for repairing the damaged heart. However, the underlying mechanisms that control stem cell mediated cardiac cell fate decisions are still poorly understood. Since GATA-4 and MEF2C are the critical regulators of cardiac differentiation, use of these factors for transfection of mesenchymal stem cells (MSCs) may enhance the potential of these stem cells for cardiac differentiation.

Research objectives

Considering the critical role of cardiac transcription factors in maintaining the structure and function of the heart during the development process, their role in cardiac differentiation is highly anticipated. These genetically modified MSCs could be a promising future therapeutic option for heart diseases.

Research methods

Human umbilical cord-MSCs (hUC-MSCs) were isolated and characterized morphologically and immunologically. The cord derived MSCs were identified by the presence of specific markers via immunocytochemistry and flow cytometry, and by their potential for osteogenic and adipogenic differentiation. hUC-MSCs were transfected with GATA-4, MEF2C, and their combination to direct cardiac differentiation. Cardiac differentiation was confirmed by semiquantitative real-time polymerase chain reaction and immunocytochemistry.

Research results

GATA-4, MEF2C, and their combination induced the differentiation of hUC-MSCs with significant expression of cardiac genes and proteins. Moreover, myotube like structure, which is the main characteristic of cardiomyocytes, was also observed in the transfected cells.

Research conclusions

Overexpression of GATA-4 and MEF2C in hUC-MSCs induces the differentiation of stem cells into cardiac-like cells. This study is an attempt to provide deeper insights into the mechanism of trans-cription factors in the cardiac differentiation of stem cells.

Research perspectives

The knowledge of the current study offers a promising therapeutic approach to improve treatment strategies for heart diseases. The genetically modified MSCs may serve as an ideal source for cardiac tissue repair and regeneration.