title: Discrepant Results of Experimental Human Mesenchymal Stromal Cell Therapy after Myocardial Infarction: Are Animal Models Robust Enough?
abstract: BACKGROUND
  Human mesenchymal stromal cells (MSCs) have been reported to preserve cardiac function in myocardial infarction (MI) models. Previously, we found a beneficial effect of intramyocardial injection of unstimulated human MSCs (uMSCs) on cardiac function after permanent coronary artery ligation. In the present study we aimed to extend this research by investigating the effect of intramyocardial injection of human MSCs pre-stimulated with the pro-inflammatory cytokine interferon-gamma (iMSCs), since pro-inflammatory priming has shown additional salutary effects in multiple experimental disease models.
  
  
  METHODS
  MI was induced in NOD/Scid mice by permanent ligation of the left anterior descending coronary artery. Animals received intramyocardial injection of uMSCs, iMSCs or PBS. Sham-operated animals were used to determine baseline characteristics. Cardiac performance was assessed after 2 and 14 days using 7-Tesla magnetic resonance imaging and pressure-volume loop measurements. Histology and q-PCR were used to confirm MSC engraftment in the heart.
  
  
  RESULTS
  Both uMSC and iMSC therapy had no significant beneficial effect on cardiac function or remodelling in contrast to our previous studies.
  
  
  CONCLUSIONS
  Animal models for cardiac MSC therapy appear less robust than initially envisioned.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Melina C
authors.initials: MC
authors.lastname: den Haan
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.|Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Vanessa-Leigh
authors.initials: VL
authors.lastname: van Zuylen
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Niek J
authors.initials: NJ
authors.lastname: Pluijmert
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Cindy I
authors.initials: CI
authors.lastname: Schutte
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schalij
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Helene
authors.initials: H
authors.lastname: Roelofs
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Douwe E
authors.initials: DE
authors.lastname: Atsma
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*