Abstract 519: Increased Growth Factors are Associated with Attenuation of Experimental Autoimmune Myocarditis by Transplantation of Bone Marrow Cells in Rats
Background: Although acute myocarditis is a fatal disease and a major cause of dilated cardiomyopathy, an effective treatment has not established yet. We examined the effect of mesenchymal stem cell (MSC) transplantation in experimental autoimmune myocarditis (EAM) rats.
Methods and Results: Lewis rats were immunized on day 0 with purified porcine cardiac myosin to establish EAM. Approximately 5 × 106/200 μl MSCs, which were obtained from Lewis rats, were directly injected in EAM rat hearts on day 14 (group 1), day 21 (group 2), and day 28 (group 3), respectively. On day 30, histological examination and echocardiogram were performed to evaluate the severity of the myocarditis. LVFS in all 3 groups (57.5±4.0% in group 1, 59.5±4.1% in group 2, and 52.8±8.1% in group 3) showed greater improvement than those of vehicle control EAM rats (40.7±2.5%, 40.3±3.1%, 44.3±4.3%, respectively). The ratios of myocarditis-affected areas in left ventricles, determined by hematoxylin and eosin staining of the heart sections, were significantly less in group 1 (26.5±10.9%) and 2 (32.2±12.5%) compared with vehicle control groups (43.2±7.3%, 42.3±5.3%). The groups with MSC transplantations showed increased capillary densities in the heart compared with vehicle control groups. The mRNA and protein expressions of VEGF and HGF in the heart were also increased in groups with MSC transplantations. The expressions of Th-1 and Th-2 cytokines were suppressed by MSC transplantations. These results suggest that enhanced expressions of VEGF and HGF attenuated myocarditis by inducing angiogenesis and suppressing the inflammatory cytokines.
Conclusions: We showed that the MSC transplantation is effective for treatment of EAM rat heart. The increased secretions of growth factors from MSCs were suggested to play an important role in improvement of EAM.