title: Human Mesenchymal Stromal Cells Improve Cardiac Perfusion in an Ovine Immunocompetent Animal Model.
abstract: BACKGROUND
  Mesenchymal stromal cells (MSCs) hold considerable promise in the treatment of ischemic heart disease. Most preclinical studies of MSCs for acute myocardial infarction (AMI) have been performed either in syngeneic animal models or with human cells in xenogeneic immunodeficient animals. A preferable pre-clinical model, however, would involve human MSCs in an immunocompetent animal.
  
  
  METHODS
  AMI was generated in adult sheep by inducing ischemia reperfusion of the second diagonal branch. Sheep (n = 10) were randomized to receive an intravenous injection of human MSCs (1 × 10(6) cells/kg) or phosphate buffered saline. Cardiac function and remodeling were evaluated with echocardiography. Perfusion scintigraphy was used to identify sustained myocardial ischemia. Interaction between human MSCs and ovine lymphocytes was assessed by a mixed lymphocyte response (MLR).
  
  
  RESULTS
  Sheep receiving human MSCs showed significant improvement in myocardial perfusion at 1 month compared with baseline measurements. There was no change in ventricular dimensions in either group after 1 month of AMI. No adverse events or symptoms were observed in the sheep receiving human MSCs. The MLR was negative.
  
  
  CONCLUSIONS
  The immunocompetent ovine AMI model demonstrates the clinical safety and efficacy of human MSCs. The human cells do not appear to be immunogenic, further suggesting that immunocompetent sheep may serve as a suitable pre-clinical large animal model for testing human MSCs.
authors.affiliation: a Faculty of Medicine, Department of Medical Pathology , University of the Republic of Uruguay , Montevideo , Uruguay.
authors.forename: Victor
authors.initials: V
authors.lastname: Dayan
authors.affiliation: b Faculty of Veterinary , University of the Republic of Uruguay , Montevideo , Uruguay.
authors.forename: Veronica
authors.initials: V
authors.lastname: Sotelo
authors.affiliation: b Faculty of Veterinary , University of the Republic of Uruguay , Montevideo , Uruguay.
authors.forename: Valentina
authors.initials: V
authors.lastname: Delfina
authors.affiliation: b Faculty of Veterinary , University of the Republic of Uruguay , Montevideo , Uruguay.
authors.forename: Natalia
authors.initials: N
authors.lastname: Delgado
authors.affiliation: b Faculty of Veterinary , University of the Republic of Uruguay , Montevideo , Uruguay.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodriguez
authors.affiliation: c Faculty of Medicine, Department of Nuclear Medicine , University of the Republic of Uruguay, Montevideo , Uruguay.
authors.forename: Carol
authors.initials: C
authors.lastname: Suanes
authors.affiliation: c Faculty of Medicine, Department of Nuclear Medicine , University of the Republic of Uruguay, Montevideo , Uruguay.
authors.forename: María
authors.initials: M
authors.lastname: Langhain
authors.affiliation: c Faculty of Medicine, Department of Nuclear Medicine , University of the Republic of Uruguay, Montevideo , Uruguay.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Ferrando
authors.affiliation: d Cell Therapy Program, Princess Margaret Hospital , University Health Network, University of Toronto , Toronto , Canada.
authors.forename: Armand
authors.initials: A
authors.lastname: Keating
authors.affiliation: b Faculty of Veterinary , University of the Republic of Uruguay , Montevideo , Uruguay.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Benech
authors.affiliation: a Faculty of Medicine, Department of Medical Pathology , University of the Republic of Uruguay , Montevideo , Uruguay.
authors.forename: Cristina
authors.initials: C
authors.lastname: Touriño
mesh_terms: D000328:Adult; D000818:Animals; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004452:Echocardiography; D064368:Healthy Volunteers; D006801:Humans; D007275:Injections, Intravenous; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000601:surgery*; D055414:Myocardial Perfusion Imaging; D011897:Random Allocation; D015427:Reperfusion Injury / Q000000981:diagnostic imaging / Q000601:surgery*; D012756:Sheep; D014183:Transplantation, Heterologous
keywords: animal model; myocardial ischemia; stem cells