Effects of bone marrow mesenchymal stem cell transplantation transfected with vascular endothelial growth factor gene on angiogenesis in rat myocardial infarcted area

Wenwu ZHOU; Jiping GAO; Liping LI

ABSTRACT

BACKGROUND:

Bone marrow mesenchymal stem cells (BMSCs) as a genetic carrier are beneficial to keep a genetic stability of exogenous gene. BMSCs can transfer human vascular endothelial growth factor (hVEGF) gene into the myocardial infarcted area. It is possible to obtain a cooperation of gene and cell therapy.

OBJECTIVE:

To investigate the angiogenesis at myocardial infarcted area of rats undergoing the transplantation of BMSCs transfected with hVEGF gene and in vivo expression of VEGF gene. DESIGN, TIME AND

SETTING:

A randomized control experiment was performed at the Institute of Paediatrics of Hunan Children's Hospital and Central Laboratory of Xiangya Second Hospital of Central South University from 2004 to 2007. MATERIALS Male clean inbred strain Wistar rats were selected in the study. Rat models of myocardial infarction were established by ligation of coronary artery.

METHODS:

BMSCs were harvested from rats by density gradient centrifugation and adherent culture. Plasmid PeDNA3. 1-hVEGF 165 were transfected at 80%-90% cell confluence. Rat models of myocardial infarction, constructed by ligation of the left anterior descending coronary artery, were randomly divided into 4 groups. 2 weeks after the ligation,BMSCs transfected with hVEGF gene were injected into rat models in the combination group at the myocardial infarction zone. BMSCs were injected into cell group. Liposome-pcDNA3.1-VEGF165 DNA compound was injected into gene group. Culture medium was injected into control group. MAIN OUTCOME

MEASURES:

Capillary density and VEGF gene expression in the myocardial infarcted area of rats in each group four weeks after injection.

RESULTS:

Capillary density was the highest at rat myocardial infarcted area in the combination and gene groups, followed by the cell group (P=0.001, 0.029) and the control group (P=0.028).Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that the hVEGF165 gene was expressed in the combination, gene, cell and control groups from higher level to lower level in order.

CONCLUSION:

BMSCs as the vector of VEGF gene are beneficial to its stable expression.Transplantation of BMSCs transfected with hVEGF gene is helpful for angiogenesis at myocardial infarcted area of rats. Its outcome is better than gene or cell therapy alone.