骨髓基质细胞移植于缺血心肌的研究

Experimental studies on bone marrow stromal cells (BMSCs) transplantation into the ischemic myocardium

国家自然科学基金资助项目 ( 30 170 935)目的 研究骨髓基质细胞移植于缺血心肌后的分化增殖情况和对心功能的保护作用。方法 以同基因背景的Lewis大鼠为研究对象 ,将溴氮胞苷 (BrdU)标记的骨髓基质细胞移植于结扎冠状动脉的大鼠缺血心肌内 ,4周后观察移植细胞的分化增殖情况和促血管生长作用 ,并用超声检测心功能改变。结果 细胞移植 4周后 ,可以在缺血心肌内找到BrdU标记的移植细胞 ,其中相当一部分细胞已分化为肌浆球蛋白重链 (MHC)阳性的心肌细胞。另外IIIV因子染色可见实验组移植区内有大量的血管新生 (2 3± 4/HPF) ,而对照组中却很少发现 (2± 1 /HPF) ,差异有非常显著性 (P <0 .0 1 )。超声检查显示移植骨髓基质细胞后可显著改善缺血心脏功能 ,其中实验组动物射血分数 (EF)升高了 0 .2 51± 0 .1 0 3 ,而对照组却降低了 0 .0 94± 0 .0 0 3 ,差异有非常显著性 (P<0 .0 1 )。结论 骨髓基质细胞移植于缺血心肌后可以向心肌细胞转化 。

Objective To study the hypothesis that bone marrow stromal cells (BMSCs), when implanted into myocardium, can undergo proliferation and differentiation and improve the heart function.Methods Adult Lewis rats, a kind of isogenic rats, were used as tested animals. BMSCs labeled with BrdU were transplanted into the infarcted myocardium whose corresponding coronary arteries have been ligated. BMSCs's proliferation and differentiation and their angiogenic function 4 weeks later were observed. Ultrasound was also used to detect their effects on heart function.Results Four weeks after transplantation, the BrdU labeled BMSCs could be found in host myocardium. The majority of them had been differentiated into cardiomyocytes with the expression of myosin heavy chain. In addition, the positive staining of ⅢⅤ factor indicated there were a great deal of neovascularation in host area (23±4/HPF), while a little in control group (2±1/HPF) (P<0.01). Echocardiography indicated that the heart function had a great improvement after BMSCs transplantation. Ejective fraction (EF) was increased from 0.458±0.063 to 0.709±0.137 in transplantation group, while it was decreased from 0.428± 0.176 to 0.334±0.161 in control group (P<0.01).Conclusion BMSCs can be differentiated into viable cardiomyocytes when transplanted into infarcted myocardium and can improve the heart function remarkably.