Guo Changfa, Haider Husnain Kh, Shim Winston S N, Tan Ru-San, Ye Lei, Jiang Shujia, Law Peter K, Wong Philip, Sim Eugene K W
Department of Surgery, National University of Singapore, Singapore.
J Thorac Cardiovasc Surg. 2007 Nov;134(5):1332-9. doi: 10.1016/j.jtcvs.2007.07.025.
We sought to investigate immune cell kinetics in relation to skeletal myoblast survival and heart function improvement after nonautologous skeletal myoblast transplantation in a rat model of myocardial infarction.
One week after myocardial infarction, 208 Wistar rats were grouped into group 1 (n = 24, receiving 150 muL of medium only), group 2 (n = 24, receiving 150 muL of medium and cyclosporine [INN: ciclosporin]), group 3 (n = 40, human skeletal myoblast transplantation), group 4 (n = 40, human skeletal myoblast transplantation with cyclosporine treatment), group 5 (n = 40, rat skeletal myoblast transplantation), and group 6 (n = 40, rat skeletal myoblast transplantation with cyclosporine treatment). The hearts were harvested at 10 minutes and 1, 4, 7, and 28 days after cell transplantation. Skeletal myoblast survival was confirmed by means of immunohistochemical studies and quantified by using real-time polymerase chain reaction. Host immune responses were assessed by immunostaining for macrophages and CD4+ and CD8+ lymphocytes. Heart function was evaluated by means of echocardiographic analysis.
The majority of macrophages and lymphocytes infiltrated in the acute phase (from day 1 to day 7) and then subsided by day 28. The donor skeletal myoblasts survived and differentiated well in all skeletal myoblast transplantation groups. Allogeneic skeletal myoblasts showed a superior survival rate than xenogeneic skeletal myoblasts (P < .01). Cyclosporine inhibited the infiltration of the immunocytes, enhanced skeletal myoblast survival, and improved heart performance compared with that seen in the groups not receiving cyclosporine treatment (P < .05).
Allomyoblasts survive better than do xenomyoblasts after transplantation into infarcted myocardium. After inhibition of immunocyte infiltration by means of immunosuppressive treatment, skeletal myoblast survival is enhanced, with improved heart performance. These findings suggest the feasibility of nonautologous myoblast transplantation with immunosuppressive treatment.
我们试图在心肌梗死大鼠模型中，研究非自体骨骼肌成肌细胞移植后免疫细胞动力学与骨骼肌成肌细胞存活及心脏功能改善之间的关系。
心肌梗死后1周，将208只Wistar大鼠分为1组（n = 24，仅接受150 μL培养基）、2组（n = 24，接受150 μL培养基和环孢素[国际非专利药品名称：环孢菌素]）、3组（n = 40，人骨骼肌成肌细胞移植）、4组（n = 40，人骨骼肌成肌细胞移植并接受环孢素治疗）、5组（n = 40，大鼠骨骼肌成肌细胞移植）和6组（n = 40，大鼠骨骼肌成肌细胞移植并接受环孢素治疗）。在细胞移植后10分钟以及1、4、7和28天收获心脏。通过免疫组织化学研究确认骨骼肌成肌细胞存活，并使用实时聚合酶链反应进行定量。通过对巨噬细胞以及CD4 +和CD8 +淋巴细胞进行免疫染色来评估宿主免疫反应。通过超声心动图分析评估心脏功能。
大多数巨噬细胞和淋巴细胞在急性期（第1天至第7天）浸润，然后在第28天消退。在所有骨骼肌成肌细胞移植组中，供体骨骼肌成肌细胞存活并分化良好。同种异体骨骼肌成肌细胞的存活率高于异种骨骼肌成肌细胞（P <.01）。与未接受环孢素治疗的组相比，环孢素抑制了免疫细胞的浸润，提高了骨骼肌成肌细胞的存活率，并改善了心脏功能（P <.05）。
同种异形成肌细胞移植到梗死心肌后比异种异形成肌细胞存活更好。通过免疫抑制治疗抑制免疫细胞浸润后，骨骼肌成肌细胞存活率提高，心脏功能改善。这些发现表明非自体成肌细胞移植联合免疫抑制治疗具有可行性。
