Mesenchymal Stem Cells Pretreatment With Stromal-Derived Factor-1 Alpha Augments Cardiac Function and Angiogenesis in Infarcted Myocardium

Am J Med Sci. 2021 Jun;361(6):765-775. doi: 10.1016/j.amjms.2021.01.025. Epub 2021 Feb 12.

Abstract

Background: Stem cell therapy is among the novel approaches for the treatment of post-myocardial infarction cardiomyopathy. This study aims to compare the effect of stromal-derived factor 1 α (SDF1α), mesenchymal stem cells (MSCs) in combination with the lentiviral production of vascular endothelial growth factor (VEGF) on infarct area, vascularization and eventually cardiac function in a rat model of myocardial infarction (MI).

Methods: The influence of SDf1α on MSCs survival was investigated. MSCs were transduced via a lentiviral vector containing VEGF. After that, the effect of mesenchymal stem cell transfection of VEGF-A165 and SDf1α preconditioning on cardiac function and scar size was investigated in five groups of MI rat models. The MSC survival, cardiac function, scar size, angiogenesis, and lymphocyte count were assessed 72 hours and 6 weeks after cell transplantation.

Results: SDF1α decreased the lactate dehydrogenase release in MSCs significantly. Also, the number of viable cells in the SDF1α-pretreated group was meaningfully more than the control. The left ventricular systolic function significantly enhanced in groups with p240MSC, SDF1αMSC, and VEGF-A165MSC in comparison to the control group.

Conclusions: These findings suggest that SDF1α pretreatment and overexpressing VEGF in MSCs could augment the MSCs' survival in the infarcted myocardium, reduce the scar size, and improve the cardiac systolic function.

Keywords: MSC; Myocardial infarction; Myocardial injection; SDF1α pre conditioning; VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chemokine CXCL12 / administration & dosage*
  • Male
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / physiology
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / therapy*
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / physiology
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / administration & dosage

Substances

  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Recombinant Proteins