TNF-alpha enhances engraftment of mesenchymal stem cells into infarcted myocardium

Front Biosci (Landmark Ed). 2009 Jan 1;14:2845-56. doi: 10.2741/3417.


TNF-alpha released from ischemic heart after acute MI increases the production of other cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). Activation of nuclear factor kappa B (NF-kappa B) by TNF-alpha , up-regulates the expression of molecules which are involved in inflammation and cell adhesion. For these reasons, we assessed the extent that treatment of MSC with tumor necrosis factor (TNF)-alpha modifies the characteristics of MSC, important to their engraftment in experimental myocardial infarct. Here, we show that pre-treatment of MSC prior to transplantation with tumor necrosis factor (TNF)-alpha increases adhesiveness, and migration of MSC in vitro and leads to increased expression of bone morphogenetic protein (BMP)-2 by MSC. Moreover, this treatment increases the rate of engraftment of MSC and improves recovery of cardiac function after myocardial infarction. These insights might provide better strategies for the treatment of myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Bone Morphogenetic Protein 2 / physiology
  • Cell Transplantation
  • Collagen / metabolism
  • DNA Primers
  • Enzyme-Linked Immunosorbent Assay
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • NF-kappa B / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / physiology
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Bone Morphogenetic Protein 2
  • DNA Primers
  • NF-kappa B
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • Tumor Necrosis Factor-alpha
  • Collagen