title: eNOS overexpressing bone marrow cells are safe and effective in a porcine model of myocardial regeneration following acute myocardial infarction.
abstract: OBJECTIVE
  Cell therapy has been shown to be effective in improving LV function postmyocardial infarction (MI). We hypothesized that eNOS-transfected bone marrow cells (BMCs) are safe in a swine model of myocardial infarction (MI). We also hypothesized that endothelial nitric oxide synthase (eNOS) transfection would enhance cell function, as assessed by myocardial functional recovery post-MI.
  
  
  METHODS
  Fifteen female Yorkshire pigs underwent bone marrow aspiration and creation of MI. Bone marrow cells were cultured for 7 days, and each pig received either autologous BMCs transiently transfected with eNOS plasmid (eNOS-BMC, n = 5), nontransfected BMCs (nt-BMC, n = 4), or phosphate-buffered saline (PBS) control (n = 6). Cardiac MRI was performed at baseline (1 week post-MI) and 6 weeks post-MI.
  
  
  RESULTS
  There was no difference in safety outcomes between groups. Absolute left ventricular ejection fraction (LVEF) at 6 weeks showed a trend toward improvement in both cell therapy groups compared with baseline but worsened in the PBS control group. The absolute improvement in LVEF was significantly greater in both cell therapy groups compared with PBS control. Infarct mass was significantly lower in the eNOS-BMC group between baseline and 6 weeks, but the absolute change in infarct mass was not different between groups. Finally, there was a trend toward reduced LV mass in the eNOS-BMC group.
  
  
  CONCLUSIONS
  Bone marrow cell delivery, with and without eNOS overexpression, is safe and leads to improvement in LVEF when administered in the coronary circulation 7 days following acute MI in swine. Transfection of healthy BMCs with eNOS resulted in some improvement in left ventricular remodeling. Further study is warranted in a preclinical model that approximates the impact of cardiovascular risk factors on BMC function.
authors.affiliation: Keenan Research Centre of the LI-Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ward
authors.forename: Kim A
authors.initials: KA
authors.lastname: Connelly
authors.forename: Ram
authors.initials: R
authors.lastname: Vijayaraghavan
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Vaags
authors.forename: John J
authors.initials: JJ
authors.lastname: Graham
authors.forename: Warren
authors.initials: W
authors.lastname: Foltz
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Hough
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: Alexander
authors.initials: A
authors.lastname: Dick
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology*; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D005260:Female; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000502:physiology*; D012038:Regeneration; D013552:Swine; D016277:Ventricular Function, Left
chemical_list: D052250:Nitric Oxide Synthase Type III
keywords: Interventional cardiology; Ischemic heart disease; Molecular cardio-biology; Vascular biology