VEGF enhances functional improvement of postinfarcted hearts by transplantation of ESC-differentiated cells

Stem Cell Research Laboratory, The Charles A. Dana Research Institute and Harvard-Thorndike Laboratory, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215 Despite considerable advances in medicine, the incidence...

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Published in:	Journal of applied physiology (1985) 2002-09, Vol.93 (3), p.1140-1151
Main Authors:	Yang, Yinke, Min, Jiang-Yong, Rana, Jamal S, Ke, Qingen, Cai, Jingbo, Chen, Yu, Morgan, James P, Xiao, Yong-Fu
Format:	Article
Language:	eng
Subjects:	Animals Biological and medical sciences Biotechnology Cell Differentiation Cells, Cultured Endothelial Growth Factors - genetics Endothelial Growth Factors - metabolism Endothelial Growth Factors - therapeutic use Fundamental and applied biological sciences. Psychology Gene therapy Health. Pharmaceutical industry Heart - physiopathology Heart attacks Industrial applications and implications. Economical aspects Intercellular Signaling Peptides and Proteins - genetics Intercellular Signaling Peptides and Proteins - metabolism Intercellular Signaling Peptides and Proteins - therapeutic use Lymphokines - genetics Lymphokines - metabolism Lymphokines - therapeutic use Mice Myocardial Contraction Myocardial Infarction - pathology Myocardial Infarction - physiopathology Myocardial Infarction - therapy Myocardium - pathology Rodents Stem Cell Transplantation Stem cells Stem Cells - cytology Stem Cells - metabolism Transfection Transplants & implants Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors
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Summary:	Stem Cell Research Laboratory, The Charles A. Dana Research Institute and Harvard-Thorndike Laboratory, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215 Despite considerable advances in medicine, the incidence of heart failure remains high in patients after myocardial infarction (MI). This study investigated the effects of engrafted early-differentiated cells (EDCs) from mouse embryonic stem cells, with or without transfection of vascular endothelial growth factor (VEGF) cDNA (phVEGF 165 ), on cardiac function in postinfarcted mice. EDCs were transfected with green fluorescent protein (GFP) cDNA and transplanted into infarcted myocardium. Compared with the MI mice receiving cell-free medium, cardiac function was significantly improved in the MI mice 6 wk after transplantation of EDCs. Moreover, improvement of heart function was significantly greater in the mice implanted with EDCs overexpressing VEGF (EDCs-VEGF) than with EDCs alone. Frozen sections of infarcted myocardium with EDCs or EDCs-VEGF transplantation showed GFP-positive tissue. The area with positive immunostaining for cardiac troponin I and -myosin heavy chain was larger in injured myocardium with EDCs or EDCs-VEGF transplantation than with medium injection. Transplantation of EDCs or EDCs-VEGF significantly increased the number of blood vessels in the MI area. However, the density of capillaries was significantly higher in the EDCs-VEGF animals than in the EDC mice. Double staining for GFP and connexin-43 was positive in injured myocardium with EDC transplantation. Our data demonstrate that engrafted EDCs or EDCs-VEGF regenerated cardiac tissue and significantly improved cardiac function in postinfarcted hearts. The novel EDCs-VEGF synergistic approach may have an important impact on future cell therapy for patients experiencing MI or heart failure. embryonic stem cells; vascular endothelial growth factor; myocardial infarction; cell transplantation
ISSN:	8750-7587 1522-1601