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. 2020 Oct 13;15(4):983–998. doi: 10.1016/j.stemcr.2020.09.002

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© 2020 The Authors

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

PMC Copyright notice

Cell Line-Specific Differences in Drug Responses

Examples of the most prominent differences in drug responses between cell lines.

(A) Relative change in force in response to BayK-8644 (C25: n = 5, AT1: n = 6, PLU: n = 4, CDI: n = 4, COR: n = 4, ICE, n = 6, CEL and NCR: n = 4, loss of after drug administration, see Figure S2). Note difference in effect size.

(B) Relative change in force in response to nifedipine (C25: n = 6, AT1: n = 6, PLU: n = 4, CDI: n = 3, COR: n = 4, ICE, n = 5, CEL: n = 4, NRC: n = 5). Note >10-fold differences in sensitivity.

(C) Relative change in RT_80% in response to EMD-57033 (C25: n = 6, AT1: n = 6, PLU: n = 4, CDI: n = 3, COR: n = 4, ICE, n = 5, CEL: n = 2, NCR: n = 4). Note the unusual shortening of relaxation in PLU.

(D) Relative change in RT_80% in response to isoprenaline (C25: n = 5, PLU: n = 7, CDI: n = 6, COR: n = 4, CEL: n = 6, NCR: n = 5). Note absence of lusitropic effect in most cell lines.

(E and F) Relative change TTP_−80% and RT_80% in response to thapsigargin (C25: n = 6, AT1: n = 6, PLU: n = 4, CDI: n = 3, COR: n = 4, ICE: n = 6, CEL: n = 4, NCR: n = 5). Note large differences in effect size ranging from no effect to >2-fold.

(G and H) Relative change in TTP_−80% and RT_80% in response to ryanodine (C25: n = 6, AT1: n = 5, PLU: n = 3, CDI: n = 3, COR: n = 3, ICE, n = 5, CEL: n = 3, NCR: n = 5). Note large differences in effect size and diverging effects on RT. Please note differences in scaling of the graph axes. For statistical analysis please see Table S3. A-H: All data represent mean ± SEM.

(I) Success of drug screening. Expected drug effects on force, TTP and RT are indicated in the respective first column (in gray, literature) and results observed for the respective cell lines in the following. Number coding: 2 = increase, 1 = no change, 0 = decrease of parameter, LOC = loss of capture – no results available. Color coding: green = canonical effect in congruence with literature (human ventricular muscle strips as gold standard), red = not-canonical response. Please note that “success” was visually evaluated from average contraction peaks shown in Figure 5 as they compile more detailed information than the narrow parameters listed in Table S3 alone.

(J) Classification of cell lines based on QC parameters and drug screening results with heatmap coloring indicating good performance in green and less ideal results in red.