title: Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model.
abstract: BACKGROUND
  Bone marrow-derived stem cells are under investigation as a treatment for ischemic heart disease. Mesenchymal stem cells (MSCs) have been used preferentially in the acute ischemia model; data in the chronic ischemia model are lacking.
  
  
  RESULTS
  Twelve dogs underwent ameroid constrictor placement. Thirty days later, they received intramyocardial injections of either MSCs (100x10(6) MSCs/10 mL saline) (n=6) or saline only (10 mL) (controls) (n=6). All were euthanized at 60 days. Resting and stress 2D echocardiography was performed at 30 and 60 days after ameroid placement. White blood cell count (WBC), C-reactive protein (CRP), creatine kinase MB (CK-MB), and troponin I levels were measured. Histopathological and immunohistochemical analyses were performed. Mean left ventricular ejection fraction was similar in both groups at baseline but significantly higher in treated dogs at 60 days. WBC and CRP levels were similar over time in both groups. CK-MB and troponin I increased from baseline to 48 hours, eventually returning to baseline. There was a trend toward reduced fibrosis and greater vascular density in the treated group. MSCs colocalized with endothelial and smooth muscle cells but not with myocytes.
  
  
  CONCLUSIONS
  In a canine chronic ischemia model, MSCs differentiated into smooth muscle cells and endothelial cells, resulting in increased vascularity and improved cardiac function.
authors.affiliation: Texas Heart Institute at St Luke's Episcopal Hospital, Houston, Tex 77030, USA.
authors.forename: Guilherme V
authors.initials: GV
authors.lastname: Silva
authors.forename: Silvio
authors.initials: S
authors.lastname: Litovsky
authors.forename: Joao A R
authors.initials: JA
authors.lastname: Assad
authors.forename: Andre L S
authors.initials: AL
authors.lastname: Sousa
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Martin
authors.forename: Deborah
authors.initials: D
authors.lastname: Vela
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Coulter
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Judy
authors.initials: J
authors.lastname: Ober
authors.forename: William K
authors.initials: WK
authors.lastname: Vaughn
authors.forename: Rodrigo V C
authors.initials: RV
authors.lastname: Branco
authors.forename: Edie M
authors.initials: EM
authors.lastname: Oliveira
authors.forename: Rumin
authors.initials: R
authors.lastname: He
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Geng
authors.forename: James T
authors.initials: JT
authors.lastname: Willerson
authors.forename: Emerson C
authors.initials: EC
authors.lastname: Perin
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis; D002454:Cell Differentiation; D019070:Cell Lineage; D003331:Coronary Vessels / Q000166:cytology / Q000473:pathology; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form; D004285:Dogs; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology*; D005260:Female; D005355:Fibrosis; D015552:Injections, Intralesional; D007527:Isoenzymes / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D017202:Myocardial Ischemia / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D018919:Neovascularization, Physiologic; D009928:Organ Specificity; D010641:Phenotype; D013318:Stroke Volume; D019210:Troponin I / Q000097:blood; D014463:Ultrasonography
chemical_list: D007527:Isoenzymes; D019210:Troponin I; D002097:C-Reactive Protein; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form