HO-1 gene overexpression enhances the beneficial effects of superparamagnetic iron oxide labeled bone marrow stromal cells transplantation in swine hearts underwent ischemia/reperfusion: an MRI study.
To determine the effect of intracoronary transfer of superparamagnetic iron oxide (SPIO) labeled heme oxygenase-1 (HO-1) overexpressed bone marrow stromal cells (BMSCs) in a porcine myocardial ischemia/reperfusion model. Cell apoptosis was assayed and supernatant cytokine concentrations were measured in BMSCs that underwent hypoxia/reoxygen in vitro. Female mini-swines that underwent 1 h LAD occlusion followed by 1 h reperfusion were randomly allocated to receive intracoronary saline (control), 1 x 10(7) SPIO-labeled BMSCs transfected with pcDNA3.1-Lacz plasmid (Lacz-BMSCs), pcDNA3.1-human HO-1 (HO-1-BMSCs), pcDNA3.1-hHO-1 pretreated with a HO inhibitor, tin protoporphyrin (SnPP, n = 10 each). MRI and postmortem histological analysis were made at 1 week or 3 months thereafter. Post hypoxia/reoxygen in vitro, apoptosis was significantly reduced, supernatant VEGF significantly increased while TNF-alpha and IL-6 significantly reduced in HO-1-BMSCs group compared with Lacz-BMSCs group (all p < 0.05). Myocardial expression of VEGF was significantly higher in HO-1-BMSCs than in Lacz-BMSCs group at 1 week post transplantation (all p < 0.05). Signal voids induced by the SPIO were detected in the peri-infarction region in all BMSC groups at 1 week but not at 3 months post transplantation and the extent of the hypointense signal was the highest in HO-1-BMSCs group, and histological analysis showed that signal voids represented cardiac macrophages that engulfed the SPIO-labeled BMSCs. Pretreatment with SnPP significantly attenuated the beneficial effects of HO-1-BMSCs. Transplantation of HO-1-overexpressed BMSCs significantly enhanced the beneficial effects of BMSCs on improving cardiac function in this model.
Jiang
Yibo
Y
Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, People's Republic of China.
Chen
Lijuan
L
Tang
Yaoliang
Y
Ma
Genshan
G
Shen
Chengxing
C
Qi
Chunmei
C
Zhu
Qi
Q
Yao
Yuyu
Y
Liu
Naifeng
N
D000818:Animals; D017209:Apoptosis; D016026:Bone Marrow Transplantation / Q000473:pathology*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D005290:Ferric Compounds; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D013552:Swine; D013556:Swine, Miniature; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology
D016207:Cytokines; D005290:Ferric Compounds; D042461:Vascular Endothelial Growth Factor A; C000499:ferric oxide; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1