Abstract 15044: Cardiac Explant-derived Cells From Aged Donors With Ischemic Cardiomyopathy Demonstrate Impaired Cell Survival and Therapeutic Regeneration
Bibliographic record
Abstract
Background: While cardiac stem cells are emerging as a promising therapy for ischemic cardiomyopathy (ICM), the influence of advanced donor age and ICM on the regenerative performance of these cells are unknown. Hypothesis: Advanced donor age and a history of ICM combine to limit the regenerative performance of explant-derived cells (EDCs) through altered cell functions which reflects fundamental changes in the molecular signature of aged ischemic EDCs. Methods and Results: EDCs were cultured from myocardial biopsies of young (8 weeks; n=40) and old (52 weeks; n=36) C57/BL6 mice 4 weeks after randomization to sham or experimental myocardial infraction (MI; ejection fraction 28±2%, p=0.24 effect of donor age). Although advanced donor age was associated with reduced telomere length, aging alone had negligible effects on EDCs. In contrast, EDCs sourced from aged ICM donors showed reduced cardiomyogenic differentiation (i.e., greater propensity to adopt an endothelial or smooth muscle lineage), cytokine production (reduced angiogenin, angiopoietin-1 and VEGF), pro-angiogenic capacity (1.2±0.03 fold less tubules formed; p=0.02), reactive oxygen species metabolism (1.8±0.3 fold greater reactive oxygen species, p=0.04; 1.9±0.1 fold less superoxide dismutase activity, p<0.01; 2.4±0.3 fold less glutathione peroxidase activity, p<0.01), and apoptosis resistance (1.5±0.1 fold greater; p=0.02) as compared to young ICM EDCs. With the exception of 1.6±0.1 fold greater production of IL-6 (p=0.04), ICM did not influence young EDCs. Transplantation of EDCs from aged ICM donors into aged recipients 1 week after MI provided lesser degrees of cell-mediated cardiac repair (3±1 vs. 8±1% change in LVEF from baseline to 21 days post CSC transplant after transplant of young ICM EDCs; p<0.01). Finally, transcriptome comparison of ICM EDCs showed aging promoted the differential expression of 145 genes (≥2 fold change; false discovery rate ≤0.05) which modify many of the pathways responsible for effective cell cycle control and DNA damage/repair. Conclusions: EDCs from aged donors with a history of ICM demonstrate an attenuated capacity for cardiac repair that reflects differential expression of transcripts suggestive of impaired cell cycle control and repair.
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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) | 0.000 | 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 | 0.001 |
| 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".