Copyright © 2006, European Society of Cardiology
The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model
aDepartment of Cardiovascular Medicine, The Heart Center of Chonnam National University Hospital, 8 Hak Dong, Dong Ku, Gwangju 501-757, South Korea
bResearch Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, South Korea
cCardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, USA
* Corresponding author. Tel.: +82 62 220 4764; fax: +82 62 223 3105. Email address: cecilyk{at}hanmail.net
Objective This study was designed to examine whether mesenchymal stem cells (MSCs) transduced with Akt enhance cardiac repair after transplantation into the ischemic porcine heart.
Methods MSCs isolated from porcine bone marrow and transduced with myr-Akt were transplanted into porcine hearts after experimental myocardial infarction (MI) using intracoronary injection [Group I, vehicle; Group II, MSCs; Group III, Akt-MSCs]. Myocardial single photon emission tomography (M-SPECT) was performed to assess myocardial function and the infarcted area. Pigs were also sacrificed for immunohistochemical characterization and histologic analysis. In addition, in vitro assays were performed to examine the resistance of Akt-MSCs to H2O2 stimulation.
Results Transplantation of MSCs into the ischemic porcine myocardium (Group II) increased the left ventricular ejection fraction (
LV EF; – 6.3±15.1% versus 0.5±6.4%, P<0.001) and decreased the area of MI (6.8±5.6% versus – 5.0±5.3%, P<0.001) compared with the vehicle control (Group I). Transplantation of MSCs transduced with myr-Akt (Group III) resulted in further improvement in LV EF (– 6.3±15.1% versus 5.8±11.3%, P<0.001) and in area of MI (6.8±5.6% versus – 17.0±7.6%, P<0.001). Akt-MSCs were more resistant to apoptosis, and the levels of extracellular signal-regulated protein kinase (ERK) activation and vascular endothelial growth factor (VEGF) were higher in H2O2-stimulated Akt-MSCs.
Conclusion Cellular transplantation of Akt-MSCs further enhances the repair of injured myocardium compared to MSC transplantation alone by increasing the number of viable MSCs after cellular transplantation.
KEYWORDS Mesenchymal stem cell; Akt; Myocardial infarction; Porcine
1 These authors contributed equally to this work.
Time for primary review 29 days
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