Plasmid-based transient human stromal cell-derived factor-1 gene transfer improves cardiac function in chronic heart failure

Gene Ther. 2011 Sep;18(9):867-73. doi: 10.1038/gt.2011.18. Epub 2011 Apr 7.


We previously demonstrated that transient stromal cell-derived factor-1 alpha (SDF-1) improved cardiac function when delivered via cell therapy in ischemic cardiomyopathy at a time remote from acute myocardial infarction (MI) rats. We hypothesized that non-viral gene transfer of naked plasmid DNA-expressing hSDF-1 could similarly improve cardiac function. To optimize plasmid delivery, we tested SDF-1 and luciferase plasmids driven by the cytomegalovirus (CMV) promoter with (pCMVe) or without (pCMV) translational enhancers or α myosin heavy chain (pMHC) promoter in a rodent model of heart failure. In vivo expression of pCMVe was 10-fold greater than pCMV and pMHC expression and continued over 30 days. We directly injected rat hearts with SDF-1 plasmid 1 month after MI and assessed heart function. At 4 weeks after plasmid injection, we observed a 35.97 and 32.65% decline in fractional shortening (FS) in control (saline) animals and pMHC-hSDF1 animals, respectively, which was sustained to 8 weeks. In contrast, we observed a significant 24.97% increase in animals injected with the pCMVe-hSDF1 vector. Immunohistochemistry of cardiac tissue revealed a significant increase in vessel density in the hSDF-1-treated animals compared with control animals. Increasing SDF-1 expression promoted angiogenesis and improved cardiac function in rats with ischemic heart failure along with evidence of scar remodeling with a trend toward decreased myocardial fibrosis. These data demonstrate that stand-alone non-viral hSDF-1 gene transfer is a strategy for improving cardiac function in ischemic cardiomyopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CXCL12 / genetics*
  • Chronic Disease
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Genetic Vectors / metabolism
  • Heart Failure / genetics
  • Heart Failure / physiopathology
  • Heart Failure / therapy*
  • Myocardial Infarction / therapy
  • Myocardial Ischemia / therapy
  • Myocardium
  • Neovascularization, Physiologic
  • Plasmids*
  • Promoter Regions, Genetic
  • Rats
  • Rats, Inbred Lew
  • Stromal Cells / metabolism
  • Time Factors


  • Chemokine CXCL12