Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Transplantation. 2011 Feb 27;91(4):425-31. doi: 10.1097/TP.0b013e3182052bca.
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.
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).
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-γ 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.
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.
同种细胞治疗存在患者安全性和供体细胞质量控制等局限性。因此，开发和评估使用同种异体细胞的程序非常重要。我们研究了同种异体骨骼肌母细胞（SMB）移植对急性心肌梗死的影响，包括免疫反应、供体细胞存活和治疗效果。
雌性 Lewis 大鼠接受近端左前降支冠状动脉结扎。15 分钟后，它们接受主要组织相容性（MHC）匹配的 Lewis SMB 移植（S 组）和 MHC 不匹配的 ACI SMB 移植（A 组），或用缓冲液注射作为对照（C 组）。
流式细胞术显示 SMB 在体外表达 MHC 抗原和 B7 信号分子。在 A 组中，移植后 7 天白细胞介素-2 受体和干扰素-γ的转录水平显著增加，并且供体 SMB 周围的区域被 CD4 和 CD8 阳性细胞强烈浸润。估计受体左心室腔中供体细胞的数量表明，除了第 0 天外，A 组的供体 SMB 数量较少，并且消失速度更快。超声心动图显示 A 组的射血分数（EF）低于 S 组。
同种异体 MHC 不匹配的 SMB 移植到梗死心肌中会引起免疫反应和供体细胞清除加速，降低治疗效果。供体细胞存活和炎症可能在 SMB 移植治疗急性心肌梗死的治疗机制中发挥重要作用。
