Abstract P179: Human Peripheral Blood B Cells Improve Cardiac Function in Aged Rats After Myocardial Infarction

Abstract

Background: Aging is associated with increased mortality following acute myocardial infarction (AMI). Early cell therapy clinical trials for AMI have shown a modest improvement in cardiac function. Previous evidence suggest that B cells may be protective in tissue injury. Our initial studies showed that intramyocardial delivery of bone marrow derived B cells improves cardiac function in young rats. Aim: In this study, we determined the effect of B cell therapy in aged animals subjected to AMI using a clinically relevant protocol. Methods: Human PB B cells were isolated from buffy coats using CD19+ selection. Young (8-10wks) and aged (10-12mos) athymic rats had baseline echocardiography then coronary artery ligation (d1). At d7, rats had repeat echocardiography and received 1×10 7 B cells or vehicle intravenously. At d9 and d21, rats underwent follow-up echocardiography. Explanted hearts were measured for infarct size and B cell localization was determined in infarcted aged rat hearts after d8 in a subset of animals by IHC. Results: Fractional ventricular diameter shortening (FS) decreased at d7 compared to baseline in young (27.9 ±0.9 vs. 55.6±0.6%, P <0.001) and aged (31.6±0.9 vs. 53.4±0.5%, P <0.001) rats. At d9, FS was higher in B cell compared to control treated aged rats (44.9±2.6 vs. 29.3±3.0%, P <0.001). FS was minimally changed in B cell compared to control treated young rats (37.3±3.3 vs. 31.2±3.5%, P =NS). At d21, FS was higher in aged rats receiving B cells compared to controls (38.6±2.2 vs. 30.0±2.6%, P <0.001) and trended higher in B cell treated young rats compared to control (34.1±1.8 vs. 28.0±2.6%, P =0.058). FS was higher in aged rats receiving B cells stored for 1.5hrs at room temperature compared to freshly prepared B cells (35.1±3.2% vs. 27.1±2.4%, P =0.035). Infarct size was smaller in B cell treated aged rats compared to controls (12.9±2.3 vs. 22.4±2.4% LV, P =0.010); no difference in infarct size was detected in young rats. B cells were detected in the infarct of aged rats at d8. Conclusion: These data support that intravenous delivery of peripheral blood B cells is efficacious in improving cardiac function and limiting infarct size in aged rats, an experimental model more relevant to clinical population.