Myocardial regeneration by transplantation of modified endothelial progenitor cells expressing SDF-1 in a rat model

J Cell Mol Med. 2012 Oct;16(10):2311-20. doi: 10.1111/j.1582-4934.2012.01539.x.

Abstract

Cell based therapy has been shown to attenuate myocardial dysfunction after myocardial infarction (MI) in different acute and chronic animal models. It has been further shown that stromal-cell derived factor-1α (SDF-1α) facilitates proliferation and migration of endogenous progenitor cells into injured tissue. The aim of the present study was to investigate the role of exogenously applied and endogenously mobilized cells in a regenerative strategy for MI therapy. Lentivirally SDF-1α-infected endothelial progenitor cells (EPCs) were injected after 90 min. of ligation and reperfusion of the left anterior descending artery (LAD) intramyocardial and intracoronary using a new rodent catheter system. Eight weeks after transplantation, echocardiography and isolated heart studies revealed a significant improvement of LV function after intramyocardial application of lentiviral with SDF-1 infected EPCs compared to medium control. Intracoronary application of cells did not lead to significant differences compared to medium injected control hearts. Histology showed a significantly elevated rate of apoptotic cells and augmented proliferation after transplantation of EPCs and EPCs + SDF-1α in infarcted myocardium. In addition, a significant increased density of CD31(+) vessel structures, a lower collagen content and higher numbers of inflammatory cells after transplantation of SDF-1 transgenic cells were detectable. Intramyocardial application of lentiviral-infected EPCs is associated with a significant improvement of myocardial function after infarction, in contrast to an intracoronary application. Histological results revealed a significant augmentation of neovascularization, lower collagen content, higher numbers of inflammatory cells and remarkable alterations of apoptotic/proliferative processes in infarcted areas after cell transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cardiac Catheterization / methods
  • Cell Proliferation
  • Chemokine CXCL12 / genetics*
  • Chemokine CXCL12 / metabolism
  • Collagen / metabolism
  • Echocardiography
  • Endothelial Cells / metabolism
  • Endothelial Cells / transplantation*
  • Female
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • In Situ Nick-End Labeling
  • Inflammation / pathology
  • Lentivirus
  • Models, Animal
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy
  • Myocardium / metabolism*
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / therapy
  • Rats
  • Rats, Sprague-Dawley
  • Regeneration*
  • Spleen / cytology
  • Spleen / metabolism
  • Stem Cell Transplantation
  • Stem Cells / metabolism*

Substances

  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Collagen