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

J Appl Physiol (1985). 2002 Sep;93(3):1140-51. doi: 10.1152/japplphysiol.00307.2002.

Abstract

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 alpha-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.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / metabolism
  • Endothelial Growth Factors / therapeutic use*
  • Heart / physiopathology*
  • 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
  • Stem Cell Transplantation*
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Transfection
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors