Therapeutic effect of transplantation of bone marrow mesenchymal stem cells over-expressing Cx43 on heart failure in post-infarction rats

Abstract

To explore the therapeutic effect of transplantation of bone marrow mesenchymal stem cells (BMSCs) over-expressing Cx43 on heart failure in post-infarction rats. Sixty SD rats were randomly divided equally into 4 groups: sham group, DMEM/F12 group injected with DMEM/F12, EGFP group with transplanted EGFP transfected BMSCs and Cx43 group with transplanted Cx43 transfected BMSCs. Myocardial infarction model was established by ligating anterior descending branch and the cells were transplanted after 30 minutes. At Week 4 post-infarction, the heart functions of rats were evaluated by echocardiography. After the rats were sacrificed, their tissue samples were collected. The areas of myocardial infarction and the levels of collagen fiber content were measured. And the expressions of EGFR and Cx43 were observed under laser confocal microscopy. The level of Cx43 mRNA was measured by reverse transcription-polymerase chain reaction (RT-PCR). As compared with the DMEM/F12 group, cardiac function was improved significantly, myocardial infarct area shrunk and collagen fiber content decreased significantly in the EGFP and group in Cx43 groups the. Survival of BMSCs and the formation of gap junction between BMSCs and the host myocardium could be observed under laser confocal microscopy both in EGFP group and Cx43 groups. And the post-infarction, expression of Cx43 mRNA in myocardial tissue decreased significantly in the group DMEM/F12, when compared with sham group (0.18 ± 0.05 vs 0.78 ± 0.14, P < 0.01). There was no significant difference on expression of Cx43 mRNA between DMEM/F12 group and EGFP group (0.18 ± 0.05 vs 0.20 ± 0.09, P > 0.05). The lever of Cx43 mRNA was higher in group Cx43 than in group DMEM/F12 and group EGFP(0.39 ± 0.14 vs 0.18 ± 0.05, P < 0.01; 0.39 ± 0.14 vs 0.20 ± 0.09, P < 0.05). Transplantation of BMSCs attenuates ventricular remodeling and improves cardiac functions. It may result from the over-expression of Cx43 gene through its effects of improving gap junction remodeling and increasing electro-mechanical coupling between myocardial cells in peri-infarct area.