Abstract 16677: Allogeneic Cardiospheres Boost Cardiac Function and Attenuate Adverse Remodeling Without Eliciting Immune Reactions Post-Myocardial Infarction in Immunologically-Mismatched Rat Strains
BACKGROUND: Autologous cardiospheres, 3-dimensional heart-derived multicellular structures that form spontaneously in suspension culture, have been shown to ameliorate remodeling and improve global function after intramyocardial (IM) injection in infarcted pig hearts. However, autologous tissue processing is fraught with considerable expense, delays to treatment and potential complications.The possible role of allogeneic cardiospheres in restoring ischemic heart tissue has not been studied.
OBJECTIVES: We evaluated the immunologic profile of syngeneic and allogeneic cardiospheres in vitro and their in vivo efficacy after IM injection in a rat model of acute myocardial infarction.
METHODS: Cardiospheres expanded from male Wistar Kyoto (WKY) rat hearts were injected in the peri-infarct zone of WKY female (syngeneic group, n=18) or Brown Norway female rats (allogeneic group, n=20). Brown Norway female rats (n=12) injected with normal saline served as controls.
RESULTS: In vitro, cardiospheres expressed only MHC I antigens on their outer layer, while MHC II were only gradually expressed after stimulation with γ-interferon over a course of 7 days. In vivo, cell engraftment was equivalent in the two treated groups 1 week (syngeneic 4.5% vs allogeneic 3%, p>0.05) and 3 weeks after injection (<0.5% in both groups). At the same time points, infarct size was significantly and equally reduced in the two cardiosphere-treated groups compared with the vehicle-treated group by quantitative morphometry. Echocardiography revealed similar functional improvement in both cardiosphere-treated groups at one week (EF syngeneic 45.5±2.9, allogeneic 46.4 ± 1.7 vs control 33.4±1.7, p<0.05 ) and three weeks of follow up (EF syngeneic 51.5±1.9, allogeneic 50.5±2.2 vs control 31.9±0.7, p<0.05). Histopathologic evaluation of the infarct site and the peri-infarct zone, where the allogeneic cardiospheres were injected, showed no signs of rejection.
CONCLUSION: Allogeneic cardiospheres engraft in the infarcted heart, improve cardiac function and limit infarct size, to the same extent as syngeneic ones, without evident immune reaction. Cardiospheres may serve as an effective off-the-shelf cell product for regeneration after acute myocardial infarction.
- © 2011 by American Heart Association, Inc.