Abstract 404: Deterministic Paracrine Repair of Injured Myocardium using Microfluidic Cocooning of Heart Explant-Derived Cells
Bibliographic record
Abstract
Previous work has shown that cocooning heart explant-derived cells (EDCs) within protective nanoporous gel capsules before intra-myocardial injection increases the retention of transplanted cells and the paracrine production of nanoparticles to improve post infarct cardiac function. In this study, we investigated the influence of cocoon size and intracapsular cell number on cell-treatment outcomes using a newly developed microfluidic-based (MF) cellular cocooning platform. Methods/Results: Traditional vortex-based encapsulation (Vx) inherently provides cocoons of varying diameters (30-100 μm; 68±5 μm). By altering the flow pressure ratios and the nozzle diameters within the MF chip, we encapsulated human EDCs within small (51±1 μm, MF50) and large (90±1 μm, MF90) diameter nanoporous gel cocoons for comparison with standard Vx-defined capsules (71±1 μm, MF70). MF cocooning mirrored the expected Poisson distribution with smaller cocoons having a greater proportion of single cells while larger diameter cocoons contained greater proportions of multicellular aggregates. Immunodeficient mice underwent left coronary artery ligation 1 week before randomization to echocardiographic guided intra-myocardial injection of EDCs (suspended or variable diameter cocoons) or vehicle. Increasing cocoon diameter stimulated progressive salutary effects on post-infarct function (ejection fraction), scar burden and newly generated peri-infarct blood vessels (isolectin B4+) and cardiomyocytes (BrdU+/TNT+) 4 weeks after treatment. Bioluminescent imaging of luciferase tagged cells revealed increasing cocoon diameter reduced the rate of cell clearance from injured tissues. Disrupting cell-cell contact within the capsules (using a custom antibody cocktail to block E/P-selectin and N-cadherin) reduced the amount and profile of pro-healing cytokines + nanoparticles delivered to injured myocardium. Conclusions: Increasing cocoon diameter and cell occupancy within protective nanoporous gel cocoons boosts paracrine-mediated repair of damaged myocardium by slowing clearance of cells from injured tissues and the number of cytokines + nanoparticles secreted by micro-encapsulated cells.
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 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) | 0.000 | 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) | 0.000 | 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".