Effects of combined mesenchymal stem cells and heme oxygenase-1 therapy on cardiac performance.
OBJECTIVE
Bone marrow mesenchymal stem cells (MSCs) have the potential to repair the infarcted myocardium and improve cardiac function. However, this approach is limited by its poor viability after transplantation, and controversy still exists over the mechanism by which MSCs contribute to the tissue repair.


METHODS
The human heme oxygenase-1 (hHO-1) was transfected into cultured MSCs using an adenoviral vector. 1 x 10(6) Ad-hHO-1-transfected MSCs (HO-1-MSCs) or Ad-Null-transfected MSCs (Null-MSCs) or PBS only (PBS group) were injected intramyocardially into rat hearts 1h after myocardial infarction.


RESULTS
HO-1-MSCs survived in the infarcted myocardium, and expressed hHO-1 mRNA. The expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) was significantly enhanced in HO-1-MSCs-treated hearts. At the same time, there were significant reduction of TNF-alpha, IL-1-beta and IL-6 mRNA, and marked increase of IL-10 mRNA in HO-1-MSCs-treated hearts. Moreover, a further downregulation of proapoptotic protein, Bax, and a marked increase in microvessel density were observed in HO-1-MSCs-treated hearts. The infarct size and cardiac performance were also significantly improved in HO-1-MSCs-treated hearts.


CONCLUSIONS
The combined approach improves MSCs survival and is superior to MSCs injection alone.
Zeng
Bin
B
Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei, PR China. zengbin19982005@yahoo.com.cn
Chen
Honglei
H
Zhu
Chengang
C
Ren
Xiaofeng
X
Lin
Guosheng
G
Cao
Feng
F
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection / Q000379:methods; D016896:Treatment Outcome; D020257:Ventricular Remodeling; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D016207:Cytokines; D051028:bcl-2-Associated X Protein; D051547:Heme Oxygenase-1