Cardiac cell lines (H9C2, AC16, HL-1) showed markedly lower RNA expression of cardiac markers compared to primary cells, indicating low-to-moderate similarity to mature adult cardiac tissue.
Commonly used cardiac cell lines (H9C2, AC16, HL-1) have low resemblance to mature adult cardiac tissue, limiting their translational value as models for primary cardiomyocytes.
BACKGROUND: Cardiac cell lines and primary cells are widely used in cardiovascular research. Despite increasing number of publications using these models, comparative characterization of these cell lines has not been performed, therefore, their limitations are undetermined. We aimed to compare cardiac cell lines to primary cardiomyocytes and to mature cardiac tissues in a systematic manner. METHODS AND RESULTS: Cardiac cell lines (H9C2, AC16, HL-1) were differentiated with widely used protocols. Left ventricular tissue, neonatal primary cardiomyocytes, and human induced pluripotent stem cell-derived cardiomyocytes served as reference tissue or cells. RNA expression of cardiac markers (e.g. Tnnt2, Ryr2) was markedly lower in cell lines compared to references. Differentiation induced increase in cardiac- and decrease in embryonic markers however, the overall transcriptomic profile and annotation to relevant biological processes showed consistently less pronounced cardiac phenotype in all cell lines in comparison to the corresponding references. Immunocytochemistry confirmed low expressions of structural protein sarcomeric alpha-actinin, troponin I and caveolin-3 in cell lines. Susceptibility of cell lines to sI/R injury in terms of viability as well as mitochondrial polarization differed from the primary cells irrespective of their degree of differentiation. CONCLUSION: Expression patterns of cardiomyocyte markers and whole transcriptomic profile, as well as response to sI/R, and to hypertrophic stimuli indicate low-to-moderate similarity of cell lines to primary cells/cardiac tissues regardless their differentiation. Low resemblance of cell lines to mature adult cardiac tissue limits their potential use. Low translational value should be taken into account while choosing a particular cell line to model cardiomyocytes.
Onódi et al. (Fri,) conducted a other in Cardiac cell models. Cardiac cell lines (H9C2, AC16, HL-1) vs. Primary cardiomyocytes and mature cardiac tissues was evaluated on Expression patterns of cardiomyocyte markers, whole transcriptomic profile, and response to sI/R and hypertrophic stimuli. Cardiac cell lines (H9C2, AC16, HL-1) showed markedly lower RNA expression of cardiac markers compared to primary cells, indicating low-to-moderate similarity to mature adult cardiac tissue.