Abstract 15008: Hydrogel-Mediated Sustained Intra-Pericardial Delivery of Endothelial Colony-Forming Cells-Derived Extracellular Vesicles Promote Cardiac Repair Post-Myocardial Infarction
Bibliographic record
Abstract
Introduction: Myocardial infarction (MI) is a leading cause of death worldwide. Although available treatments improve prognosis post-MI, they do not remediate cardiomyocyte death and loss of cardiac vasculature, resulting in chronic maladaptive remodeling and subsequently, heart failure. Extracellular vesicles (EVs) derived from endothelial colony-forming cells (ECFCs) show therapeutic potential, facilitating adaptive cardiac remodeling post-MI. However, ECFCs function is compromised in patients with type-2 diabetes, a common risk factor for MI, limiting the applicability of autologous cell-based therapies. Therapeutic administration is a further challenge, as current strategies present difficulties regarding invasiveness, retention, and efficacy. Hypothesis: We hypothesized that the minimally invasive intra-pericardial (IP) injection of ECFCs-EVs within a hydrogel would improve cardiac retention and promote sustained therapeutic release, facilitating cardiac repair in a murine model of MI. We anticipated that this repair would be greater with the use of EVs derived from wildtype mice than from diabetic mice. Methods: The impact of wildtype and diabetic ECFCs-EVs was evaluated on both in vitro EVs retention and angiogenesis. In a murine model of MI, the left anterior descending coronary artery was ligated while the pericardium was preserved. We evaluated whether IP injection is an effective and safe method of delivering hydrogels containing ECFCs-EVs, in addition to its long-term effects on cardiac morphology and function. Results: Our findings indicate that hydrogel use facilitates sustained EVs release. Besides that, the administration of ECFCs-EVs increased coronary endothelial cell proliferation, migration, and vascularization in vitro, and reduced maladaptive cardiac remodeling, improving cardiac contractility and function in vivo. These effects appear to be more pronounced with the administration of wildtype ECFCs-EVs. Conclusions: Collectively, our results underscore the therapeutic promise of ECFCs-EVs to improve cardiac repair after MI.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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) | 0.000 | 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 teacher head, 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".