Overexpression of Csx/Nkx2.5 and GATA-4 enhances the efficacy of mesenchymal stem cell transplantation after myocardial infarction.

Abstract

BACKGROUND:

The high death rate of the transplanted stem cells in the infarcted heart and low efficiency of differentiation toward cardiomyocytes show that mesenchymal stem cell (MSC) transplantation after myocardial infarction (MI) is not effective. Csx/Nkx2.5 and GATA-4 are considered to be key regulators of cardiogenesis. The aim of the present study was to investigate the effect of transplanting MSC overexpressing Csx/Nkx2.5 and GATA-4 (MSCs-CG) after MI.

METHODS AND RESULTS:

According to acridine orange/ethidium bromide staining, MSCs-CG were more resistant to anoxia as compared with MSCs in vitro. In a mouse MI model, ejection fraction and fractional shortening were higher in the MSC-CG group than in the MSC or phosphate-buffered saline group. Wall thickness of the infarct area was increased and collagen deposition was clearly reduced in the MSC-CG group as compared with the other groups. There were more surviving MSCs in the MSC-CG group than in the MSC group. Most of the Y chromosome-positive cells expressed cardiac troponin T and connexin43 (Cx-43). Cx-43 was localized between Y chromosome-positive cells and recipient cardiomyocytes. Microvessel density in the peri-infarct regions and infarct regions increased significantly in the MSC-CG group.

CONCLUSIONS:

Transplantation of MSCs overexpressing Csx/Nkx2.5 and GATA-4 represents a new treatment strategy with the potential to improve cardiac function after MI.

• Authors: Xi-Ren Gao, Yu-Zhen Tan, Hai-Jie Wang
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 75 Issue 11 Pg. 2683-91 ( 2011) ISSN: 1347-4820 [Electronic] Japan
• PMID: 21828931 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Connexin 43
• GATA4 Transcription Factor
• Gata4 protein, mouse
• Homeobox Protein Nkx-2.5
• Homeodomain Proteins
• Nkx2-5 protein, mouse
• Transcription Factors
• Troponin T

Topics

• Animals
• Connexin 43 (biosynthesis, genetics)
• Female
• GATA4 Transcription Factor (biosynthesis, genetics)
• Gene Expression
• Homeobox Protein Nkx-2.5
• Homeodomain Proteins (biosynthesis, genetics)
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (metabolism)
• Mice
• Myocardial Infarction (genetics, pathology, physiopathology, therapy)
• Myocardium (metabolism, pathology)
• Stroke Volume
• Transcription Factors (biosynthesis, genetics)
• Transplantation, Homologous
• Troponin T (biosynthesis, genetics)