title: Reparative effects of allogeneic mesenchymal precursor cells delivered transendocardially in experimental nonischemic cardiomyopathy.
abstract: OBJECTIVE
  This study set out to evaluate the safety and efficacy of allogeneic bone marrow mesenchymal precursor cells (MPC) delivered by multisegmental, transendocardial implantation in the setting of nonischemic cardiomyopathy (NICM).
  
  
  BACKGROUND
  Prospectively isolated MPC have shown capacity to mediate cardiovascular repair in myocardial ischemia. However, their efficacy in NICM remains undetermined.
  
  
  METHODS
  Mesenchymal precursor cells were prepared from ovine bone marrow by immunoselection using the tissue nonspecific alkaline phosphatase, or STRO-3, monoclonal antibody. Fifteen sheep with anthracycline-induced NICM were assigned to catheter-based, transendocardial injections of allogeneic MPC (n = 7) or placebo (n = 8), under electromechanical mapping guidance. Follow-up was for 8 weeks, with end points assessed by cardiac magnetic resonance, echocardiography, and histology.
  
  
  RESULTS
  Intramyocardial injections were distributed similarly throughout the left ventricle in both groups. Cell transplantation was associated with 1 death late in follow-up, compared with 3 early deaths among placebo animals. Left ventricular end-diastolic size increased in both cohorts, but MPC therapy attenuated end-systolic dilation and stabilized ejection fraction, with a nonsignificant increase (37.3 ± 2.8% before, 39.2 ± 1.4% after) compared with progressive deterioration after placebo (38.8 ± 4.4% before, 32.5 ± 4.9% after, p < 0.05). Histological outcomes of cell therapy included less fibrosis burden than in the placebo group and an increased density of karyokinetic cardiomyocytes and myocardial arterioles (p < 0.05 for each). These changes occurred in the presence of modest cellular engraftment after transplantation.
  
  
  CONCLUSIONS
  Multisegmental, transendocardial delivery of cell therapy can be achieved effectively in NICM using electromechanical navigation. The pleiotropic properties of immunoselected MPC confer benefit to nonischemic cardiac disease, extending their therapeutic potential beyond the setting of myocardial ischemia.
authors.affiliation: Cardiovascular Research Centre, Royal Adelaide Hospital and Department of Medicine, University of Adelaide, Adelaide, Australia. peter.psaltis@adelaide.edu.au
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Psaltis
authors.forename: Angelo
authors.initials: A
authors.lastname: Carbone
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Nelson
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Lau
authors.forename: Troy
authors.initials: T
authors.lastname: Jantzen
authors.forename: Jim
authors.initials: J
authors.lastname: Manavis
authors.forename: Kerry
authors.initials: K
authors.lastname: Williams
authors.forename: Silviu
authors.initials: S
authors.lastname: Itescu
authors.forename: Prashanthan
authors.initials: P
authors.lastname: Sanders
authors.forename: Stan
authors.initials: S
authors.lastname: Gronthos
authors.forename: Andrew C W
authors.initials: AC
authors.lastname: Zannettino
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Worthley
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*; D004195:Disease Models, Animal; D004452:Echocardiography; D005500:Follow-Up Studies; D007273:Injections, Intramuscular; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009206:Myocardium; D012756:Sheep; D013318:Stroke Volume; D016896:Treatment Outcome; D016277:Ventricular Function, Left