Abstract 13386: Persistence of Transplanted Explant-derived Human Cardiac Stem Cells Contributes to Therapeutic Regeneration of Injured Mycardium
Bibliographic record
Abstract
Introduction: Cardiac stem cells (CSCs) mediated improvements in cardiac function have been attributed to the rescue of reversibly damaged tissue, proliferation of endogenous cells and differentiation of transplanted CSCs into new myocardium. Despite evidence that CSC therapy improves post-ischemic function, controversy surrounds the extent to which physical incorporation and persistence of transplanted cells contributes to the benefits of CSC therapy. In this study, we use “on demand” ablation of transplanted CSCs to dissect the contribution of engrafted cells to myocardial repair. Methods/Results: Diphtheria toxin (DT) was used to induce transplanted human cell death. Human CSCs were cultured from atrial appendage biopsies obtained during clinically-indicated surgery. Exposure of human CSCs to DT prompted expression of annexin V ± propidium iodide in 37±10% of treated cells within 12 hours (p≤0.05 vs. human CSCs not exposed to DT) and resulted in a progressive decline in viable human cell counts (Figure A); suggesting that DT may provide the ideal means of ablating transplanted human sourced cells within a DT resistant host. The influence of short term persistence of transplanted CSCs was investigated in a series of SCID mice by applying DT or vehicle 1 week after intra-myocardial injection of human CSCs (Figure B). A decline in the ejection fraction in CSC-treated mice underscores the importance of transplanted cell persistence on CSC-mediated cardiac repair. This decrease was paralleled by increases in scar size (1.4±1.0 fold greater % scar, p=0.05), reduced contractility (1.2±0.1 fold lower dP/dT max, p=0.04) and impaired relaxation (1.6±0.2 fold lower dP/dT min, p=0.05) as compared to mice that received CSCs alone. Conclusions: Elimination of CSCs 1 week after transplantation reduces CSC-mediated cardiac repair- suggesting that persistent paracrine secretion and/or cell replacement contribute to the maintenance of therapeutic regeneration.
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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) | 0.003 | 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".