Abstract 16707: Human Embryonic Stem Cell-Derived Cardiomyocytes Are Safe and Improve Infarct Size and Cardiac Function in a Porcine Model of Myocardial Infarction
Bibliographic record
Abstract
Introduction: Stem cell therapy is an emerging means of stimulating cardiac repair after myocardial infarction (MI). Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) are a novel therapeutic option, with the potential for cell derived remuscularization. This study assessed the safety and efficacy of these cells, is the first to test these cells in a porcine model of MI, and used electrophysiologic (EPS) testing to evaluate potential arrhythmogenicity. Methods: Yucatan swine underwent a left anterior descending coronary artery ischemia/reperfusion protocol to form an MI. Four weeks later, either placebo (n=3) or 3 x 10 8 hESC-CMs were delivered via transendocardial stem cell injection (TESI) (n=4). All animals received immunosuppression for 2 weeks following TESI. Three uninfarcted animals received cells. Cardiac function and LV chamber volumes were measured using pressure volume catheterization and cardiac MRI at 4, 8 and 12 weeks post-TESI. Inducibility of ventricular tachycardia (VT) was tested at 4 and 12 weeks post-TESI by programmed ventricular stimulation via a catheter in the RV apex. Histology of heart tissue and organs was evaluated. Results: Twelve weeks post-TESI, scar size (scar mass as a % of total LV mass) was reduced in the cell treated group by -2.33±0.03% (p=0.034), a 12.69±1.87% reduction from pre-TESI. Scar size remained constant in the placebo group. The rise in end diastolic volume at 12 weeks in the placebo group (15.6±7.35 mL; p=0.032) was attenuated in the cell treated group (10.39±6.36mL; p=0.17). By 12 weeks post-TESI, Ees (slope of ESPVR) increased by 0.51±0.15 mmHg/mL (p=0.045) and in the cell treated group but was unchanged in placebo (-0.09±0.85 mmHg/mL; p= 0.92). Following TESI, only 1 animal from each group had inducible VT. No animals had spontaneous VT as measured by an implantable loop recorder. Cardiac function and structure of uninfarcted animals did not change over the study, and none of these animals had inducible VT. Histology did not reveal ectopic tissue formation or signs of rejection. Conclusion: TESI of hESC in a porcine MI model is safe, does not increase the risk of either spontaneous or inducible arrhythmias compared to placebo, reduces scar size and remodeling and improves cardiac contractility as measured by Ees. Translation to clinical studies is warranted.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".