Developing engineered cardiac tissue models from HL-1 cardiomyocytes and mouse embryonic fibroblasts

Engineered cardiac tissue models become increasingly important for understanding normal and diseased cardiac physiology. The use of in-vitro engineered disease models can give more insight in the changing structurefunction properties during pathological condition; therefore, contributing to the development of new cardiac therapies. It is hypothesized that during cardiac disorders of impaired mechanotransduction, the ratios of cardiomyocytes, fibroblasts and their supporting endogenous extracellular matrix (ECM) change. Furthermore, these changes are comparable and predictable of the different stages of diseased cardiac tissue. The aim of this study is to investigate the effect of different cardiomyocyte/fibroblast ratios on tissue morphology and function. Co-cultures of the HL-1 cardiomyocyte cell line and mouse embryonic fibroblasts (MEFs) at different ratios were used in 2D feasibility studies. Cyclic mechanical straining was applied to mimic cardiac tissue deformation during contraction. Both HL-1 and MEFs survived in co-culture although clustering of HL-1 cells was observed. The cluster size of HL-1 was dependent on the amount of MEFs. Mechanical stimulation of cultures showed strain avoidance response of MEFs while co-culture with HL-1 prevented this response. The data obtained provides new insights in the usefulness of cardiac cell-line-derived HL-1 and MEFs in the development of cardiac tissue models.