Research Alert
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.
Key Words: Heart disease, GATA binding protein 4, Myocyte enhancer factor 2C, Transcription factors, Differentiation, Human umbilical cord-mesenchymal stem cells
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.
- Citation: 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
- URL: https://www.wjgnet.com/1948-0210/full/v14/i9/700.htm
- DOI: https://dx.doi.org/10.4252/wjsc.v14.i9.700