title: Mesenchymal stem cell therapy for cardiac inflammation: immunomodulatory properties and the influence of toll-like receptors.
abstract: BACKGROUND
  After myocardial infarction (MI), the inflammatory response is indispensable for initiating reparatory processes. However, the intensity and duration of the inflammation cause additional damage to the already injured myocardium. Treatment with mesenchymal stem cells (MSC) upon MI positively affects cardiac function. This happens likely via a paracrine mechanism. As MSC are potent modulators of the immune system, this could influence this postinfarct immune response. Since MSC express toll-like receptors (TLR), danger signal (DAMP) produced after MI could influence their immunomodulatory properties.
  
  
  METHODS
  Not much is known about the direct immunomodulatory efficiency of MSC when injected in a strong inflammatory environment. This review focuses first on the interactions between MSC and the immune system. Subsequently, an overview is provided of the effects of DAMP-associated TLR activation on MSC and their immunomodulative properties after myocardial infarction.
  
  
  CONCLUSIONS
  MSC can strongly influence most cell types of the immune system. TLR signaling can increase and decrease this immunomodulatory potential, depending on the available ligands. Although reports are inconsistent, TLR3 activation may boost immunomodulation by MSC, while TLR4 activation suppresses it.
  
  
  CONCLUSIONS
  Elucidating the effects of TLR activation on MSC could identify new preconditioning strategies which might improve their immunomodulative properties.
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: van den Akker
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: S C A
authors.initials: SC
authors.lastname: de Jager
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands ; ICIN-Netherlands Heart Institute, Catharijnesingel 52, 3511 GC Utrecht, The Netherlands.
authors.forename: J P G
authors.initials: JP
authors.lastname: Sluijter
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D056747:Immunomodulation; D007249:Inflammation / Q000378:metabolism*; D008024:Ligands; D008264:Macrophages / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D009000:Monocytes / Q000166:cytology; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000166:cytology; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D008024:Ligands; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors