Key result
Cardiac cell lines show markedly lower cardiac marker expression and limited similarity to primary tissue controls.
Why the study?
Limitations of commonly used cardiac cell lines to model cardiovascular diseases in vitro remain undetermined despite their widespread use.
Commonly used cardiac cell lines exhibit low-to-moderate transcriptomic and morphological similarity to primary cardiomyocytes and mature cardiac tissues, suggesting caution when using them as in vitro models.
Answers are grounded in this paper and cite their sources.
Limitations of cardiac cell lines remain undetermined; leaves open their validity for in vitro cardiovascular disease modeling.
Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union's Horizon 2020 research and innovation programme National Research, Development and Innovation Fund of Hungary Background Cardiac cell lines and primary cell cultures are widely used to model various cardiovascular diseases in vitro. Despite the increasing number of publications using these models, limitations of these cell lines are still undetermined. Purpose The aim of our study was to compare the most commonly used cardiac cell lines to primary cultures and to mature cardiac tissues by transcriptomic analysis and morphological characterization. Methods H9C2 (rat), AC16 (human) and HL-1 (mouse) cardiac cell lines were differentiated towards a phenotype more resembling cardiomyocytes, by methods most widely used in the literature, and cells were harvested at stages of proliferation and differentiation. Whole left ventricular tissue, neonatal primary cardiac myocytes isolated from mice and rats, or human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) were applied as references. Transcriptome analysis and immunocytochemical detection of cardiac structural proteins were performed on all cell models. Results RNA expression of cardiac markers (e.g. Tnnt2, Ryr2, Tnni3) was markedly lower in cell lines compared to primary cells or hiPSC-CM and adult tissue controls. Differentiation procedures induced a significant increase in cardiac- and decrease in embryonic markers in AC16 and H9C2 lines; however, the overall expression pattern of investigated genes in all cell lines showed significant differences in comparison to corresponding myocardium or primary cultures. Immunocytochemistry confirmed low expressions of structural protein alpha-actinin and troponin I in cell lines. Conclusion Expression patterns of cardiomyocyte markers and mRNA profile indicates low-to-moderate similarity of cell lines to primary cells/cardiac tissues regardless the differentiation protocol used. These limitations should be taken into account while choosing cells as in vitro platforms to model cardiomyocytes and cardiovascular diseases.
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Gulyas-Onodi et al. (2022) studied this question. Cardiac cell lines (H9C2, AC16, HL-1) vs. Primary cultures and mature cardiac tissues was evaluated on RNA expression of cardiac markers and structural proteins. Cardiac cell lines (H9C2, AC16, HL-1) demonstrated markedly lower RNA expression of cardiac markers and low-to-moderate similarity to primary cells and adult tissue controls.
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