Overexpression of Csx/Nkx2.5 and GATA-4 Enhances the Efficacy of Mesenchymal Stem Cell Transplantation After Myocardial Infarction

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概要

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• 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. (Circ J 2011; 75: 2683-2691)

• 2011-10-25

著者

• Wang Hai-jie

  Department Of Anatomy And Histology And Embryology Shanghai Medical School Of Fudan University

• Tan Yu-zhen

  Department Of Anatomy And Histology And Embryology Shanghai Medical School Of Fudan University

• Tan Yu-zhen

  Department Of Anatomy Histology And Embryology Shanghai Medical School Of Fudan University

• GAO Xi-ren

  Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University

• Wang Hai-jie

  Department Of Anatomy Histology And Embryology Shanghai Medical School Of Fudan University

• Gao Xi-ren

  Department Of Anatomy Histology And Embryology Shanghai Medical School Of Fudan University

関連論文

• Transplantation of Mesenchymal Stem Cells Preconditioned with Diazoxide, a Mitochondrial ATP-Sensitive Potassium Channel Opener, Promotes Repair of Myocardial Infarction in Rats
• Transplantation of Mesenchymal Stem Cells with Self-Assembling Polypeptide Scaffolds Is Conducive to Treating Myocardial Infarction in Rats
• Overexpression of Csx/Nkx2.5 and GATA-4 Enhances the Efficacy of Mesenchymal Stem Cell Transplantation After Myocardial Infarction

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