Human Pluripotent Stem Cell-Derived Cardiomyocytes: Response to TTX and Lidocain Reveals Strong Cell to Cell Variability
Bibliographic record
Abstract
Stem cell derived cardiomyocytes generated either from human embryonic stem cells (hESC-CMs) or human induced pluripotent stem cells (hiPSC-CMs) hold great promise for the investigation of early developmental processes in human cardiomyogenesis and future cell replacement strategies. We have analyzed electrophysiological properties of hESC-CMs (HES2) and hiPSC-CMs, derived from reprogrammed adult foreskin fibroblasts that have previously been found to be highly similar in terms of gene expression. In contrast to the similarity found in the expression profile we found substantial differences in action potentials (APs) and sodium currents at late stage (day 60) of in vitro differentiation with higher sodium currents in hiPSC-CMs. Sensitivity to lidocain was considerably reduced in hESC-CMs as compared to hiPSC-CMs, and the effect could not be explained by differences in beating frequency. In contrast, sensitivity to tetrodotoxin (TTX) was higher in hESC-CMs suggesting different contributions of TTX-sensitive and TTX-resistant sodium channels to AP generation. These data point to physiological differences that are not necessarily detected by genomics. We conclude that novel pharmacological screening-assays using hiPSC-CMs need to be applied with some caution.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".