干细胞移植改善犬心输出量和每搏量及二尖瓣功能的研究

Improvement of cardiac output stroke,volume and mitral valve function by autologous stem cell implantation after permanent coronary occlusion in canines

目的 观察自体骨骼肌干细胞———卫星细胞移植于缺血心肌后对犬心输出量 (CO)、每搏量 (SV)及二尖瓣功能的影响。方法 取 12只成年犬臀大肌 ,分离、培养、传代、二脒苯基吲哚 (DAPI)标记卫星细胞 ;将标记的卫星细胞 ,自左冠状动脉前降支结扎点远端注入已经建立的急性心肌梗死动物模型缺血心肌中。 2、4、8周后对犬CO、SV及二尖瓣功能的改变进行观察。结果 卫星细胞移植 2、4、8周后 ,实验组犬CO、SV与对照组比较 ,差异均有显著性意义。以 8周时的差异最为显著。实验组 2周及对照组 2、4、8周心脏出现室间隔中下部变薄及典型的矛盾运动 ,二尖瓣中到重度反流 ;实验组 4、8周时 ,室间隔中下部变薄 ,无矛盾运动 ,二尖瓣形态正常无反流。结论 干细胞移植可使CO及SV显著增加 ,二尖瓣功能得到显著改善。

Objective To implant autologous skeletal muscle satellite cells into ischemic myocardium to reinforce its cardiac output (CO) and stroke volume (SV) and transmitral inflow pattern.In this study a reproducible method for the creation of a myocardial lesion was developed.Methods Satellite cells isolated from the skeletal muscle of adult canines are labeled with 4',6 diamididino 2 phenylindole(DAPI),which bands to DNA and to the protein tubulin to form a fluorescent complex.A ligation of left anterodecendant artery (LAD) was carried out on a canine model to induce a well delineated transmural lesion.Thereafter,autologous skeletal muscle stem cells(experimental groups) or culture media (control groups) were infused into ventricular myocardium of isogenic canine through LAD.Two,four,and eight weeks after cell implantation,cardiac output (CO) and stroke volume (SV) and the transmitral inflow pattern were evaluated by Necon 3 Noninvasive Cardiac Output Continuous Monitor and three dimensional (3D) echocardiography (USA).Results Necon 3 Noninvasive Cardiac Output Continuous Monitor studies showed a significant improvement in global and regional left ventricular function in cell treated canines.There was significant difference in cardiac output (CO) and stroke volume (SV) between the transplantation and the control groups.Echocardiography was performed 2,4,8 weeks postoperatively.In experimental group of 2 weeks and all the 3 control groups,mitral regurgitation showed no improvement,and the middle and inferior parts of ventricular septum became thin.But mitral regurgitation improved or disappeared gradually 2 weeks later,and on the contrary,the middle and inferior parts of ventricular septum showed no significant change.Conclusions Satellite cells implanted in the myocardial lesion survived for a 2 month period and were associated with a significant functional improvement of both local and global contraction.