Abstract 5367: An Epi-Myocardial Mesenchymal Stem Cell Patch with Peritoneum Repairs Scarred Myocardium after Myocardial Infarction
The most common methods of stem cell delivery in the heart are intravenous or direct injection into infarcted area. Here we show a patch that seeded mesenchymal stem cells (MSCs) on peritoneum was placed across the epicardial surface of scarred myocardium to repair myocardial infarction. We genetically engineered male rat MSCs using ex vivo adenoviral transduction for over-expressing CXCR4/green fluorescent protein (CXCR4 group) or GFP alone (control group) or miRNA targeting CXCR4 (miRNA group). These cells were cultured in dishes containing a piece of peritoneum (20 mm2) for 5 days. One month after LAD ligation in female hearts, a patch with cultured GFP positive cells was attached to the scarred myocardium. Efficacy of cell transfer and seeding were determined by a combination of unique markers (Y-chromosome and GFP). Two months later after LAD ligation, echocardiography was performed and hearts were harvested for histological and phenotypic analysis of mobilized cells. LV fibrosis, anterior wall thickness (AWT) and blood vessel density were measured. After one month cell transplantation, the engrafted patch gradually formed a thick stratum that included newly formed vessels, undifferentiated cells and a few cardiomyocytes. Extensive regeneration and survival of GFP and Y chromosome positive cells were observed in and around the infarcted myocardium in CXCR4 group. AWT was increased from 0.6 ± 0.1 mm in untreated to 1.1 ± 0.2mm after treatment in CXCR4 group, p<0.05, but not in other groups. Fibrosis (% of LV) and heart function (ejection fraction, %) were also significantly improved in CXCR4 group (18.4 ± 2.7, 64.8 ± 2.7%, respectively) as compared with control (44.7 ± 3.8, 36.2 ± 3.7%, respectively, p<0.05). The Kaplan-Meier survival curve demonstrated an 8-week survival rat of 71% for the CXCR4 group versus 53 % for the control group, p<0.05. However, these benefit effects were completely blocked by miRNA group. Transplantation of CXCR4 overexpressing MSCs with peritoneum strengthened aneurysm, enhanced angiomyogenesis, reduced fibrosis and improved heart function after myocardial infarction. Bioengineered patches may be new therapeutic strategies for cardiac tissue regeneration.