兔骨髓间充质干细胞自体移植治疗急性心肌梗塞

Treatment of Acute Myocardial Infarction in Rabbits with Autologous Transplantation of Bone Marrow Mesenchymal Stem Cells

目的 :了解骨髓间充质干细胞 (mesenchymalstemcells ,MSCs)在缺血心肌中转化为心肌细胞并改善心功能的可行性。方法 :结扎兔左前降支制作急性心肌梗塞 (acutemyocardiuminfarction ,AMI)模型 ,骨穿抽取骨髓 ,分离、培养、扩增骨髓间充质干细胞。术后 2周进行心肌梗塞瘢痕处移植 5 溴脱氧尿嘧啶 (Bromodeoxyuridine,Br dU)标记的骨髓间充质干细胞 ,对照组注射培养基。AMI术前、AMI术后 3d及移植后 4周做超声心动图检测心功能 ,移植后 4周用导管检查法测左室压力变化 ,随后处死动物取左室标本切片 ,采用免疫荧光方法鉴定植入细胞。结果 :细胞移植组左室切片中可见BrdU染色阳性细胞即植入细胞 ,对照组未见BrdU染色阳性细胞。超声心动图检查证实MSCs移植后 4周左室收缩末期直径 (LVESD)、舒张末期直径 (LVEDD)均小于对照组 (分别为P <0 .0 1及P <0 .0 5 ) ,小轴缩短率 (△D % )、射血分数 (EF)均大于对照组 (均为P <0 .0 1 )。导管测压显示MSCs移植组左室舒张末期压 (LVEDP)低于对照组、左室压上升及下降最大速率 (±dp/dt)高于对照组 (均为P <0 .0 1 )。 结论 :缺血心肌内注射骨髓间充质干细胞可依赖组织微环境转化为心肌细胞修复梗塞心肌 ,显著改善心功能 ,可用于心肌梗塞的治疗。

Objective: To investigate the implantation of bone marrow mesenchymal stem cells (MSCs) which differentiate into cardiomyocytes in ischemic myocardium and its effect on heart function. Methods: The left anterodecendant arteries (LAD) of adult rabbits were ligated to establish animal models of acute myocardial infarction(AMI). The animals were randomly divided into implantation group and control group. Mesenchymal stem cells were isolated from bone marrow and were culture expanded. 2 weeks later the MSCs labeled with Bromodeoxyuridine (BrdU) were injected into the scar tissue in implantation group. The heart function of each rabbit was evaluated with echocardiography and catheterization. Specimens were taken 4 weeks after implantation. Histologic sections of left ventricle were stained by immunofluorescent and examined under fluorescent microscope. Results: The implanted cells were found in the MSCs group and not in the control group. Compared with control group, 4 weeks after transplantation MSCs group had shorter LVESD, LVEDD and higher EF, ±dp/dt and lower LVEDP. Conclusion: Autologous bone marrow mesenchymal stem cells can be differentiated into cardiomyocytes in vivo to repair infracted myocardium and improve the heart function. Bone marrow MSCs transplantation can be used as a therapy in rabbits with AMI.