骨髓间充质干细胞移植治疗小型猪急性心肌梗死的转归  

Outcome of Transplanted Mesenchymal Stem Cells in Swine with Myocardial Infarction

作　　者：杨珂[1] 彭朝权[1] 项鹏[2] 张成喜[1] 邹丽媛[1] 吴晓[1] 高雅[1] 康庄[3] 

机构地区：[1]中山大学附属第三医院心内科,广东广州510630 [2]中山大学干细胞与组织工程研究中心,广东广州510080 [3]中山大学附属第三医院放射科,广东广州510630

出　　处：《中山大学学报（医学科学版）》2011年第2期164-168,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省科技计划项目(2007B031508009)

摘　　要：【目的】探讨超顺磁性氧化铁(SPIO)活体动态示踪小型猪骨髓间充质干细胞(MSC)移植治疗心肌梗死的可行性。【方法】采用密度梯度离心法获取小型猪自体骨髓MSC,用携带绿色荧光蛋白(GFP)基因的慢病毒载体转染MSC,并用SPIO体外标记MSC-GFP。采用经皮球囊封堵法制备急性心肌梗死(AMI)模型,双标记的MSC经冠脉移植入小型猪心肌梗死区域,移植后24h、3周、8周在MRI下进行活体动态示踪。【结果】普鲁士蓝染色显示25μgFe/mLSPIO与0.8μL/mL阳离子脂质体联合对MSC的标记率达95%～100%,对绿色荧光蛋白的表达无影响,标记细胞仍均具备多向分化能力;冠脉移植MSC后24h,3周,8周MRI成像均可见梗死区域的室间隔有明显区别于周边组织的低信号。离体组织学检查可见心梗边缘区有普鲁士蓝染色阳性,荧光阳性细胞存在。【结论】SPIO标记MSC可在MRI成像下表现出理想的信号强度和示踪时间,SPIO活体动态示踪小型猪骨髓MSC移植治疗心肌梗死是可行的。[Objective] To investigate the feasibility of in vivo serial tracking of superparamagnetic iron oxide（SPIO）-labeled mesenchymal stem cells（MSC） for treatment of acute myocardial infarction（AMI） in swine.[Methods] After isolated by density gradient centrifugation,autologous MSC were transfected with green fluorescent protein（GFP） by lentiviral vector and labeled by SPIO.An AMI model was established by percutaneous balloon occlusion.Dual-labeled MSC were traced using serial MRI after 24 h,3 weeks,and 8 weeks of intracoronary transplantation into the MI area in swine.[Results] We demonstrate that when MSC were labeled with SPIO（25 μg Fe/mL plus 0.8 μL/mL lipofectamine） the labeling efficiency was 95%-100%,with no effects on GFP expression.Additionally,labeled MSC maintained the ability to differentiate into osteoblasts and adiptoblasts.Hypointensities detected in the interventricular septum were different from the surrounding tissue after 24 h,3 weeks,and 8 weeks of intracoronary transplantation.Both Prussian blue-and fluorescence-positive cells were histologically detected in the border zone of the MI area.[Conclusion] MSC labeled with SPIO showed optimum MRI signal intensity and tracer time.These findings demonstrate the feasibility of in vivo dynamic tracing of SPIO labeled MSC for the treatment of MI in swine.

关 键 词：超顺磁性氧化铁 间充质干细胞 小型猪 急性心肌梗死 示踪 

分 类 号：R455.2[医药卫生—运动医学] R329.2[医药卫生—治疗学]