5-氮胞苷诱导和未诱导骨髓间充质干细胞移植入梗死心肌后心功能变化的比较

Changes in cardiac function following transplantation of 5-azacytidine-induced versus non-induced bone marrow mesenchymal stem cells into infarcted myocardium

背景:已证实在体外经5-氮胞苷诱导后,骨髓间充质干细胞可向类心肌细胞转化,但移植这种经诱导的髓间充质干细胞是否更有利于急性心肌梗死后心功能改善,尚有争议。目的:对比观察经5-氮胞苷诱导和未经诱导的骨髓间充质干细胞移植入急性心肌梗死组织后心功能的变化。方法:开胸结扎左冠状动脉前降支建立新西兰兔急性心肌梗死模型,分别在心肌梗死组织周边区注射PBS,经5-氮胞苷诱导或未诱导的兔骨髓间充质干细胞。移植后3d、4周超声心动图测定左室舒张末期容积,左室收缩末期容积及射血分数以评价心功能变化。结果与结论:兔前降支结扎后,心功能明显下降;移植3d后,各组动物左室舒张末期容积、左室收缩末期容积及射血分数均无显著差异,说明无论是否在体外经5-氮胞苷诱导过,骨髓间充质干细胞移植短期对兔心功能无明显改善;移植4周后,与注射PBS的动物比较,移植骨髓间充质干细胞可降低心肌梗死兔的左室舒张末期容积、左室收缩末期容积,提高射血分数,但骨髓间充质干细胞在体外是否经5-氮胞苷诱导对心功能改善程度无影响。

BACKGROUND：Bone marrow mesenchymal stem cells （BMSCs） have the potential to differentiate into cardiomyocyte-like cells following induction of 5-azacytidine in vitro.Whether transplanted stem cells could improve cardiac function was unclear.OBJECTIVE：To compare the changes in cardiac function following transplantation of BMSCs with or without induction of 5-azacytidine into tissues of acute myocardial infarction （AMI）.METHODS：New Zealand rabbits were developed into AMI models by ligating left anterior descending artery.Phosphate buffered saline, 5-azacytidine-induced or non-induced BMSCs were separately injected into the surrounding regions of myocardial infarct tissues.Three days or four weeks after transplantation, echocardiogram was used to measure left ventricular end diastolic volume, ventricular end-systolic volume and ejection fraction to evaluate changes in cardiac function.RESULTS AND CONCLUSION：Following anterior descending branch ligation, the cardiac function was significantly decreased.At 3 days following transplantation, no significant difference was determined in left ventricular end diastolic volume, ventricular end-systolic volume and ejection fraction in each group.These suggested that transplantation of 5-azacytidine-induced and non-induced BMSCs did not affect rabbit cardiac function in a short phase.At 4 weeks following transplantation, compared with control group, transplanted BMSCs could decrease left ventricular end diastolic volume, ventricular end-systolic volume and ejection fraction.However, there were no obvious differences of cardiac function between 5-aza＋BMSCs and BMSCs transplantation.