Allogenic Skeletal Myoblast Transplantation in Acute Myocardial Infarction Model Rats
Allogenic Skeletal Myoblast Transplantation in Acute Myocardial Infarction Model Rats
复制标题
异基因骨骼肌母细胞移植在急性心肌梗死模型大鼠中的应用
DOI：
10.1097/tp.0b013e3182052bca
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发表时间：
2011-02-27
期刊：
影响因子：
6.2
通讯作者：
Sawa, Yoshiki
中科院分区：
文献类型：
--
作者：
Imanishi, Yukiko;Miyagawa, Shigeru;Sawa, Yoshiki
背景同基因细胞疗法的局限性包括患者的安全性和源细胞的质量控制。因此，重要的是开发和评估使用同种异体细胞的程序。我们研究了同种异体骨骼肌成肌细胞（SMB）移植对急性心肌梗死患者免疫应答、供体细胞存活和治疗效果的影响。雌性刘易斯大鼠接受冠状动脉左前降支近端结扎。15 min后，分别行MHC相合的刘易斯SMB移植（S组）和MHC不相合的ACI SMB移植（A组），或对照组（C组）。流式细胞仪检测显示，体外培养的SMB表达MHC抗原和B7信号分子。A组移植后7 d，IL-2受体和IFN-γ的转录水平明显升高，供者外周血淋巴细胞CD 4和CD 8阳性细胞浸润。对受体左心室腔中供体细胞数量的估计显示，与S组相比，除第0天外，A组的供体SMB较少，消失得更快。超声心动图显示A组射血分数（EF）低于S组。MHC不匹配的同种异体SMB移植在梗死心肌中诱导免疫应答和加速供体细胞清除，降低治疗效果。供者细胞存活和炎症反应可能在SMB移植治疗急性心肌梗死的机制中起重要作用。
Background. The limitations of syngenic cell therapy include patient safety and quality control of the source cells. Therefore, it is important to develop and assess procedures using allogenic cells. We investigated the impact of allogenic skeletal myoblast (SMB) transplantation on acute myocardial infarction with respect to immune response, donor cell survival, and therapeutic efficacy.Methods. Female Lewis rats underwent proximal left anterior descending coronary artery ligation. Fifteen minutes later, they underwent major histocompatibility (MHC)-matched Lewis SMB transplantation (group S) and MHC-mismatched ACI SMB transplantation (group A), or treated with buffer injection as a control (group C).Results. Flow cytometry showed that the SMBs expressed MHC antigens and B7 signal molecules in vitro. In group A, transcription levels of interleukin-2 receptor and interferon-gamma were significantly increased 7 days after transplantation, and the area surrounding the donor SMBs was intensely infiltrated with CD4- and CD8-positive cells. Estimation of the number of donor cells in the recipient left ventricular chamber revealed that except for day 0, group A had fewer donor SMBs, which disappeared faster, compared with group S. Echocardiography demonstrated that the ejection fraction (EF) of group A was lower than that of group S.Conclusion. MHC-mismatched allogenic SMB transplantation in infarcted myocardium induces the immune response and acceleration of donor cell clearance, decreasing the therapeutic effect. Donor cell survival and inflammation may play important roles in the therapeutic mechanism of SMB transplantation therapy for acute myocardial infarction.