同种异体脂肪组织源性间质干细胞移植治疗大鼠急性心肌梗死

Transplantation of exogenous adipose tissue derived mesenchymal stem cells for treatment of acute myocardial infarction in rat

目的:建立体外分离扩增脂肪组织源性间质干细胞方法,并探讨同种异体脂肪干细胞移植治疗大鼠心肌梗死的效果及可行性。方法:18只雄性SD大鼠随机分为假手术组、急性心肌梗死对照组(AMI组)及AMI+细胞移植组。分离大鼠腹部脂肪组织干细胞,体外扩增,BrdU标记后于结扎左冠状动脉前降支后1h移植入梗死心肌,移植后4周进行血流动力学检测心功能并取出心脏进行病理切片观察和免疫组织化学染色检测移植细胞在梗死心脏中的定居、存活情况。结果:大鼠腹部脂肪组织可分离培养出大量间质干细胞。细胞移植治疗组左心室收缩压高于AMI对照组(P<0.01),舒张末压显著降低(P<0.01),左心室内压最大上升、下降速率明显加快(P<0.05);病理组织切片显示梗死边缘区心肌面毛细血管计数明显增加,梗死区心肌组织内及毛细血管壁中均可见移植标记细胞。结论:脂肪组织可作为干细胞又一新的来源,同种异体脂肪干细胞移植治疗AMI有效、可行。

AIM： To establish a method of isolating, culturing the adipose tissue -derived mesenchymal stem cells in vitro and to investigate the possibility of exogenous transplanting the adipose tissue derived mesenchymal stem cells for treatment of rat acute myocardial infarction. METHODS： 18 male rats were separated randomly into 3 groups： sham surgery group （control, n = 6）, acute myocardial infarction control group （AMI, n = 6） and myocardial infarction plus cell transplantation group （AMI ＋ cell, n = 6）. The infarcted hearts were made by occlusion of left coronary artery. The mesenchymal stem cells were isolated from the rats＇ peritoneum by using digestion methods and reproduced in vitro, then the cells were labeled with BrdU and implanted into the infarcted heart of the rats. Heart functions were measured 4 weeks after implantation. The hearts were also harvested for pathological and histoimmunochemical observations to determine the survival and location of the implanted cells. RESULTS ： Plenty of mesenchymal stem cells were obtained from the adipose tissue of rats＇ peritoneum. Compared with the AMI group, the left ventricular systolic pressure in the cell therapy group was increased significantly （ P 〈 0.01 ） , the left ventricular end - diastolic pressure was decreased （ P 〈 0. 01 ） , and the ratio of the left ventricular pressure rise and decay （ ± dp/dt ） was decreased （ P 〈 0. 05 ）. The number of blood vessels was increased at the boundary of infarction site by pathological observation. The labeled cells were founded in the infarcted myocardium and the blood vessel wall. CONCLUSION： The adipose tissue is a new optional stem cell source. The methods of exogenous transplantation of adipose tissue derived mesenchymal stem cells for treatment of AMI is effective and feasible.