Abstract 4295: Different Paracrine Mediators and Response of the Host Myocardium by Cell Therapy: Direct Comparison between Skeletal Myoblasts and Bone Marrow Mononuclear Cells
Cell therapy using bone marrow mononuclear cells (BMC) or skeletal myoblasts (SMB) is an emerging therapy for treating post-infarction heart failure. Although the paracrine effect has been proposed to be a main mechanism for the therapeutic effects of this treatment, the details remain largely unknown. This study aimed to clarify the paracrine effect of cell therapy by comparing BMC and SMB injection. Three weeks after left coronary artery ligation, female wild type rats received intramyocardial injection of either BMC or SMB derived from male GFP transgenic rats or PBS only. Echocardiography demonstrated that injection of either cell type improved cardiac function compared to PBS injection at 28 days (left ventricular fractional area change: 26.7±1.7, 36.6±1.5, 33.2±1.1% in PBS, BMC, SMB groups, respectively; n=10/group, p<0.01). Poor engraftment assessed by quantitative PCR for the male-specific Sry and rare occurrence of cardiomyogenic/vasculogenic differentiation shown by histological studies suggested that the observed functional improvement was mediated by the paracrine effect. Interestingly, BMC injection markedly improved neovascularization, while SMB injection globally decreased fibrosis. Assessment of isolated cardiomyocytes showed that both BMC and SMB injection similarly reduced hypertrophy. As possible mediators of paracrine effects, realtime RT-PCR revealed upregulation of FGF2 and HGF only after BMC injection (Table⇓). Western blotting analysis demonstrated that, among signalling pathways relevant to heart failure, phosphorylation of STAT3 and ERK1/2 was specifically elevated in the BMC and SMB group, respectively. These data suggested that both BMC and SMB injection recovered post-infarction chronic heart failure via the paracrine effect. However, paracrine mediators, downstream signal transductions and consequent effects were noticeably different between cell types.