PTEN-silenced bone marrow mesenchymal stem cell transplantation for acute myocardial infarction / 中国组织工程研究

ABSTRACT

BACKGROUND:Bone marrow mesenchymal stem cel transplantation for myocardial infarction becomes popularized in recent years, but transplanted cels cannot survive and proliferate under early inflammatory reaction or local ischemia/hypoxia microenvironment, eventualy hampering the therapeutic outcomes. OBJECTIVE:To investigate the therapeutic effect of PTEN-silenced bone marrow mesenchymal stem cels on acute myocardial infarction. METHODS:(1) Bone marrow mesenchymal stem cels from Sprague-Dawley rats were randomly assigned to receive no treatment, NCsiRNA transfection using Lipofectamin2000orPTEN siRNA transfection using Lipofectamin2000. Cel growth curves were described using MTT method to detect cel cycle using flow cytometry. (2) Thirty Sprague-Dawley rats were selected to prepare myocardial infarction models that were randomized into three groups (n=10 per group) blank control, negative control and RNAi group. Six hours after modeling, bone marrow mesenchymal stem cels transfected with nothing, NCsiRNA and PTEN siRNA were respectively injected into the infarcted center of the left ventricular anterior wal in these three rat groups. After 4 weeks, al rats were subjected to cardiac function detection using echocardiography, and the survival and proliferation of bone marrow mesenchymal stem cels in the rats were observed by fluorescence microscopy. RESULTS AND CONCLUSION:Compared with the other two groups, a significant increase in the absorbance values at different culture time, the proportion of cels in S+G2phase, and the number ofbone marrow mesenchymal stem cels in the myocardial tissue was found in the RNAi group (alP< 0.05). Additionaly, the left ventricular ejection fraction and left ventricular shortening fraction were significantly reduced in the RNAi group than the blank control and negative control groups at 4 weeks after cel transplantation (P< 0.05). Bothin vivoandin vitroexperimental findings showed that PTEN silencing could effectively improve cel survival and proliferation in the infarcted myocardium. Moreover, in thein vivoexperiment, an overt improvement in rat’s cardiac function was achieved.