Transplantation of allogenetic bone marrow mesenchymal stem cells combined with vascular endothelial growth factor gene transfection for treating myocardial infarction

Jiaming ZHANG; Yongxin LU; Qiutang ZENG; Xiaobo MAO; Siyu GUAN; Xiang WANG

ABSTRACT

BACKGROUND:

Transplantation of bone marrow mesenchymal stem cell and vascular endothelial growth factor(VEGF) can promote vascular regeneration and improve heart function. However, whether the combined application is superior to single application or not is still unclear.

OBJECTIVE:

To observe the effect of allogenetic bone manow stem cells transplantation combined with VEGF transfection on vascular regeneration and heart function of rats with acute myocardial infarction.

DESIGN:

Simple sample observation was used in culturing bone marrow mesenchymal stem cell of rats; Randomized controlled animal experiment was used in cell transplantation and gene transfection.

SETTING:

Department of Cardiology, Union Hospital of Huazhong University of Science and Technology; Cardiovascular Institute of Tongji Medical College MATERIALS Totally 94 healthy male Wistar rats and expression vector PAdTrack/VEGF165 were used in this experiment.

METHODS:

This experiment was carried out at Cardiovascular Institute of Tongji Medical College between June 2004 and June 2005. ①Bone marrow mesenchymal stem cells of rats were isolated, purified and cultured in vitro, then labeled with bromodeoxyuridine(BrdU). ② Preparation , extraction, purification and identification of plasmid PAdTrack/VEGF165. ③Two weeks after coronary artery was ligated to create acute myocardial infarction model, rats were randomly divided into 4 groups (n=12 in each group) stem cell + plasmid group(50 μL BrdU-labeled bone marrow mesenchymal stem cell solution and 100 μL plasmid PAdTrack/VEGF165 were injected into the rats through multiple sites), stem cell group (50 μL bone marrow mesenchymal stem cell solution was injected through multiple sites), plasmid group (100 μL plasmid PAdTrack/VEGF165 was injected through multiple sites) , control group(100 μL serum-free DMEM was injected through multiple sites). ④ Immunohistochemistry andechocardiography were performed 4 weeks later.MAIN OUTCOME

MEASURES:

①Immunohistochemical and haematoxylin-eosin stainings were conducted in the infarcted and ischemic areas of rats in each group; ② Blood vessel counts; ③Echocardiography.

RESULTS:

Totally 48 rats entered the stage of result analysis. ① BrdUlabeled transplanted cells could be seen at the infarcted and ischemic myocardium in the stem cell+plasmid group and stem cell group. Some transplanted cells at ischemic myocardium differentiated into vascular endothelial cells and formed newborn blood capillary. ②Density of Ⅷ factor positively-stained newborn blood capillary took stem cell +plasmid group ＞ plasmid group ＞ stem cell group ＞ control group in order (all P＜ 0.01).③Wall thickness and wall motion range improved after cell transplantation and gene transfection therapy. The increased range of ejection fraction took stem cell +plasmid group ＞ stem cell group ＞ plasmid group ＞ control group in order (all P ＜ 0.01) .

CONCLUSION:

Allogenic bone marrow mesenchymal stem cell transplantation and VEGF gene transfection could further boost vascular regeneration of infarcted ischemic area and improve wall thickness and heart function of rats.