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. 2021 Jan 27;11:2391. doi: 10.1038/s41598-021-81351-z

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Cytotoxic effects of selected SMs on undifferentiated murine iPSCs and purified murine and human iPSC-CMs. (a) Dose response curves for cytotoxicity of indicated SMs on miPSCs and miPSC-CMs after 48 h of treatment with various SM concentrations. Results are shown as relative values compared to 0.05% DMSO treated cells (mean ± SD). Data for miPSCs were pooled from two (SM1, SM4, SM5), three (SM2, SM8) or six (SM6) independent experiments with 4 replicates analyzed in each. Analyses with miPSC-CMs were performed in three independent experiments for each SM. Therapeutic index (TI) was calculated by dividing the IC50 of miPSC-CMs by the IC50 of miPSCs. (b) Dose response curves for cytotoxicity of indicated SMs on human iPSCs (NP0040 cell line) and human iPSC-CMs (day 46 of differentiation) after 48 h of treatment with various SM concentrations. Results are shown as relative values compared to 0.05% DMSO treated cells (mean ± SD). Data for hiPSCs-CMs were pooled from two independent experiments with 4 replicates analyzed in each. Therapeutic index (TI) was calculated by dividing the IC50 of hiPSC-CMs by the IC50 of hiPSCs. (c) Representative images of NP0040 hiPSCs (bright-field) and hiPSC-CMs (immunofluorescence) after 48 h treatment with controls and various concentrations of indicated SMs. At the end of the treatment, hiPSC-CMs were fixed with 3% PFA and stained with antibodies against sarcomeric α-actinin (red). Nuclei were counterstained with Hoechst 33342 (blue). Images shown are digitally magnified insets from the originals taken with the 20 × objective on Axiovert 200 M microscope. Scale bars: 50 μm. See also Supplementary Figs. S2, S3 and S4.