Abstract 580: Skeletal Myoblasts and Bone Marrow-Derived Cells Enhance the Contractile Function of Isolated Failing Cardiomyocytes in Co-culture

Abstract

Cell transplantation has been shown to enhance ventricular function in heart failure. However, the low numbers of surviving transplanted cells can not explain the functional myocardial improvement directly, and the cellular mechanisms responsible remain unknown. We hypothesized that transplanted cells influence the native myocardium by paracrine mechanisms, and investigated the in vitro effects of bone marrow mononuclear cells or skeletal myoblasts on neighboring cardiomyocytes isolated from a rat model of heart failure. Myocardial infarction was induced in adult female Sprague-Dawley rats by left coronary artery ligation. Left ventricular ejection fraction after 3 weeks was 35.5 ± 2.0%. Isolated left ventricular myocytes were cultured (density 5.2 cells/mm 2 ) on their own (Control) or with either bone marrow mononuclear cells (BM, density 52 cells/mm 2 ) or skeletal myoblasts (SK, density 5.2 cells/mm 2 ). After 48 hours of culture with SK or BM cardiomyocyte relaxation speed was increased (time to 50% relaxation, in ms - Control 34 ± 6 [ 28 ]; BM 18 ± 3 [ 16 ] p < 0.05 vs Control; SK 13 ± 2 [ 20 ] p < 0.05 vs Control). The decay time course of the Ca 2+ transient, assessed by indo-1 fluorescence, was also hastened by SK (time to 50% decay, in ms – HF 22 ± 2 [ 29 ]; BM 18 ± 2 [ 17 ] ns ; SK 13 ± 1 [ 17 ] p < 0.05 vs Control). SK also increased the contraction amplitude compared to Control (sarcomere shortening, in μm - HF 0.046 ± 0.006 [ 28 ]; BM 0.055 ± 0.01 [ 16 ] ns ; SK 0.091 ± 0.014 [ 20 ] p < 0.05 vs Control). We conclude that bone marrow mononuclear cells and skeletal myoblasts enhance cardiomyocyte function in co-culture, demonstrating that paracrine mechanisms are involved. This may account for the functional improvement seen after cell transplantation.