Insulin-like growth factor 1 improves the efficacy of mesenchymal stem cells transplantation in a rat model of myocardial infarction

J Biomed Sci. 2008 Jan;15(1):89-97. doi: 10.1007/s11373-007-9207-x. Epub 2007 Sep 6.

Abstract

Background: Previous study demonstrated the improvement of cardiac function was proportional to the number of cells implanted. Therefore, increasing cell survival in the infarcted myocardium might contribute to the improvement of the functional benefit of cell transplantation.

Methods and results: MSCs were treated with IGF-1 in vitro and infused into the acute myocardial infarction rats via the tail vein. After treatment of MSCs with IGF-1 for 48 h, flow cytometric analysis showed marked enhancement of expression of CXCR4 in the cell surface. After 4 weeks of transplantation, we found 1) a greater number of engrafted MSCs arrived and survived in the peri-infarct region; 2) TnT protein expression and capillary density were enhanced; 3) LV cavitary dilation, transmural infarct thinning, deposition of total collagen in the peri-infarct region and cardiac dysfunction were attenuated.

Conclusion: 1) IGF-1 treatment has time-dependent and dose-dependent effects on CXCR4 expression in MSCs in vitro. 2) IGF-1 improves the efficacy of MSCs transplantation in a rat model of myocardial infarction mainly via enhancement of the number of cells attracted into the infarcted heart. These findings provide a novel stem cell therapeutic avenue against ischemic heart disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capillaries / pathology
  • Cell Survival / drug effects
  • Collagen / metabolism
  • Disease Models, Animal
  • Insulin-Like Growth Factor I / pharmacology*
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / pathology
  • Mesenchymal Stem Cells / physiology
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / therapy*
  • Rats
  • Receptors, CXCR4 / metabolism
  • Troponin T / biosynthesis
  • Ventricular Function, Left

Substances

  • CXCR4 protein, mouse
  • Receptors, CXCR4
  • Troponin T
  • Insulin-Like Growth Factor I
  • Collagen