PMID- 23837864
OWN - NLM
STAT- MEDLINE
DCOM- 20140919
LR  - 20131127
IS  - 1755-5922 (Electronic)
IS  - 1755-5914 (Linking)
VI  - 31
IP  - 6
DP  - 2013 Dec
TI  - eNOS overexpressing bone marrow cells are safe and effective in a porcine model 
      of myocardial regeneration following acute myocardial infarction.
PG  - e72-8
LID - 10.1111/1755-5922.12037 [doi]
AB  - AIM: 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.
CI  - (c) 2013 John Wiley & Sons Ltd.
FAU - Ward, Michael R
AU  - Ward MR
AD  - Keenan Research Centre of the LI-Ka Shing Knowledge Institute, St. Michael's 
      Hospital, Toronto, ON, Canada.
FAU - Connelly, Kim A
AU  - Connelly KA
FAU - Vijayaraghavan, Ram
AU  - Vijayaraghavan R
FAU - Vaags, Andrea K
AU  - Vaags AK
FAU - Graham, John J
AU  - Graham JJ
FAU - Foltz, Warren
AU  - Foltz W
FAU - Hough, Margaret R
AU  - Hough MR
FAU - Stewart, Duncan J
AU  - Stewart DJ
FAU - Dick, Alexander
AU  - Dick A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cardiovasc Ther
JT  - Cardiovascular therapeutics
JID - 101319630
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*enzymology
MH  - *Bone Marrow Transplantation
MH  - Disease Models, Animal
MH  - Female
MH  - Hypertrophy, Left Ventricular/etiology
MH  - Myocardial Infarction/physiopathology/*therapy
MH  - Nitric Oxide Synthase Type III/genetics/*physiology
MH  - *Regeneration
MH  - Swine
MH  - Ventricular Function, Left
OTO - NOTNLM
OT  - Interventional cardiology
OT  - Ischemic heart disease
OT  - Molecular cardio-biology
OT  - Vascular biology
EDAT- 2013/07/11 06:00
MHDA- 2014/09/23 06:00
CRDT- 2013/07/11 06:00
PHST- 2013/07/11 06:00 [entrez]
PHST- 2013/07/11 06:00 [pubmed]
PHST- 2014/09/23 06:00 [medline]
AID - 10.1111/1755-5922.12037 [doi]
PST - ppublish
SO  - Cardiovasc Ther. 2013 Dec;31(6):e72-8. doi: 10.1111/1755-5922.12037.