XIAP modified adipose-derived stem cells improve cardiac function following myocardial infarction / 中华胸心血管外科杂志

ABSTRACT

Objective We want to study the therapeutic efficiency of autologous ADMSC transplantation in myocardial infarction.And we try to find out a good way to improve the therapeutic efficiency by using the combination of gene therapy and cell therapy.Anti-apoptotic protein XIAP was selected to fight against the ischemic environment of myocardic infaction.Methods ADMSC was isolated from rat inguinal fat tissue.ADMSC was cultivated with DMEM.XIAP experession plasmid was elertco-transduced to ADMSC.The anti-apototic function of XIAP was tested by serum stavation induced apotosis.The method of ligation of the left anterior descending artery was used to prepare the Myocardial infarction model.Then rats were randomly separated into three groups to receive direct epicardial injections of normal saline,or ADMSCs cell suspension or XIAP modified ADMSCs cell suspension at five sites in central zones of myocardial infarction and border zone.Cardiac function and the infarct size were evaluated 4 weeks after ADMSCs transplantation.Results West blotting suggest that,XIAP over-expression block serum starvation induced apotosis.It showed that there are significant statistic difference among XIAP modified ADMSC transplantation group,ADMSC transplantation group and control group 4 weeks after myocardial infarction (P ＜ 0.05).Left ventricular ejection fraction(LVEF) showed a significant improvement in ADMSCs transplantation group compared to control group (P ＜0.05).Left ventricular end systolic diameter(LVDs) and left ventricular end diastolic diameter(LVDd) of ADMSCs group were smaller than control group(P ＜ 0.05).The area of myocardial infarction was significantly reduced in the ADMSCs transplantation group compared to the saline group(P ＜0.05).Compared to ADMSCs transplantation group,effect of the XIAP modified ADMSC in rats with myocardial infarction is more obvious.The reduction of LVEF of XIAP modified ADMSCs group was signific antly lower(9％) than the ADMSCs group(16％) (P ＜ 0.01).Infarction area in XIAP modified ADMSCs group(3.26 ±0.95)％ was smaller than ADMSCs group(5.17 ±2.03)％ (P ＜0.05).Conclusion Autologus ADMSC transplantation is an efficient therapeutic tool in myocardial infarction therapy.Over expression of XIAP can partly inhibit lowserum induced apotosis of ADMSC in vitro,and it can improve left ventricular function better in vivo.Over expression XIAP of ADMSC can improve the therapeutic efficiency compare to ADMSC transplantation.