Abstract 17836: The Regenerative Capacity of Explant-derived Cardiac Stem Cells Inversely Correlates With Patient Risk for Future Cardiac Events
Bibliographic record
Abstract
Background: Although recent trials have demonstrated that cardiac-derived cell products repair damaged myocardium, the influence of age and medical co-morbidities is unknown. Therefore we investigated the effect of medical comorbidities on the functional activity of human explant-derived cardiac stem cells (EDCs). Methods/Results: Human EDCs were cultured from atrial appendages obtained during cardiac surgery. The Long Term Stratification model (LTS) was chosen as the best means of discriminating between patients with few or extensive comorbidities. Increasing LTS score demonstrated a moderate negative correlation with: 1) EDC conditioned media HUVEC tubule formation (R 2 =0.53; r=-4±1, p=0.003), 2) transwell recruitment of circulating angiogenic cells (R 2 =0.48; r=-15±5, p=0.016), 3) decreased echocardiographic ejection fraction (R 2 =0.64, r=-0.7±0.2, p=0.003) and increasing scar burden (R 2 =0.59, r=-0.5±0.2, p=0.04) 3 weeks after myocardial injection of EDCs into a SCID mouse model of myocardial infarction. These effects may be attributable to LTS score dependent decreases in SDF-1 (R 2 =0.33; r=-0.2±0.1, p=0.02) or exosome (R 2 =0.59; r=-2.4±0.8X10 7 , p=0.02) content within conditioned media. Interestingly, the most abundant cytokine in EDC conditioned media (IL-6) demonstrated a positive correlation with increasing LTS scores (R 2 =0.33, r=1.2±0.5, p=0.03). Lentiviral mediated knock down of IL-6 (IL-6KD) by EDCs suggests that IL-6 supports therapeutic regeneration as intra-myocardial injection of IL-6 KD EDCs from low (<3) and high (>5) LTS score patients reduced improvements in ejection fraction by 1.4±0.1 fold (p≤0.05) while increasing scar burden by 1.3±0.1 fold (p≤0.05). Immunohistochemistry demonstrated that IL-6KD reduced newly generated BrdU+ myocytes (p=0.03 vs. scramble treated EDCs) while promoting the persistence of maladaptive myofibroblasts (p=0.01 vs. scramble treated EDCs). Conclusions: The regenerative performance of the earliest cell population cultured from human tissue declines with accumulating medical co-morbidities. This effect is associated with diminished production of pro-cardiogenic cytokines and exosomes while IL-6 plays a novel pivotal role in EDC-mediated repair of damaged myocardium.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| 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) | 0.008 | 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".