Allogenic Skeletal Myoblast Transplantation in Acute Myocardial Infarction Model Rats

Abstract

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.