The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model.
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 H(2)O(2) stimulation.


RESULTS
Transplantation of MSCs into the ischemic porcine myocardium (Group II) increased the left ventricular ejection fraction (DeltaLV EF; -6.3 +/- 15.1% versus 0.5 +/- 6.4%, P < 0.001) and decreased the Deltaarea 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 DeltaLV EF (-6.3 +/- 15.1% versus 5.8 +/- 11.3%, P < 0.001) and in Deltaarea 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 H(2)O(2)-stimulated Akt-MSCs.


CONCLUSIONS
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.
Lim
Sang Yup
SY
Department of Cardiovascular Medicine, The Heart Center of Chonnam National University Hospital, Gwangju, South Korea.
Kim
Yong Sook
YS
Ahn
Youngkeun
Y
Jeong
Myung Ho
MH
Hong
Moon Hwa
MH
Joo
Soo Yeon
SY
Nam
Kwang Il
KI
Cho
Jeong Gwan
JG
Kang
Peter M
PM
Park
Jong Chun
JC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005822:Genetic Vectors / Q000008:administration & dosage; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D007267:Injections; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D023421:Models, Animal; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000032:analysis; D013552:Swine; D014161:Transduction, Genetic / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases