Abstract 418: Ready-made Microvessels Robustly Integrate Into the Infarcted Coronary Vasculature Promoting Graft Perfusion, Enhancing Cardiac Remuscularization and Function
Bibliographic record
Abstract
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer an unprecedented opportunity to remuscularize infarcted hearts. However, the majority of hiPSC-CMs die post transplantation into the ischemic environment, limiting their regenerative potential. CM death occurs in the first few days post-transplantation due to ischemia. Attempts to promote intramyocardial vascularization (i.e. delivery of growth factors or cells) have not led to significant improvements due to poor cell retention and the long time required for new vessels to form and carry blood compared to the rapid death of transplanted CMs. Here, we used ready-made microvessels harvested from adipose tissue - that form a vasculature and carry blood within the first days post subcutaneous implantation - to re-vascularize ischemic rat hearts and improve hiPSC-CM survival. We performed left anterior descending artery ligation in immunocompromised rats to model MI. hiPSC-CMs (10 x10 6 ) with (CM+V) or without (CM-only, control) microvessels were delivered by intra-myocardial injection 2 weeks post MI. Cardiac function was assessed by echocardiography and pressure-volume loop. Delivery of microvessels from GFP rats allowed assessment of microvessel persistence. Compared to hiPSC-CM transplantation alone, microvessels promoted a 6-fold increase in hiPSC-CM survival, with reduction in scar size and a significantly superior functional recovery. While delivery of CM-only stabilized the heart preventing further fractional shortening decline, delivery of CM+V resulted in reversal of fractional shortening loss. This was supported by PV-loop data (ejection fraction: sham, ~20%; CM-only, ~31%; CM+V, ~39%; 4 wks). Moreover, microvessels showed unprecedented persistence and integration (>60%, 4 wks), resulting in 2-fold increase in vessel area and graft perfusion (as early as day 5 post-transplantation). This was achieved despite the very low number of cells (~2 x10 5 ) delivered in the form of microvessels. These findings provide a novel approach to cell-based therapies for MI whereby incorporation of ready-made microvessels can serve as a personalized delivery system to improve functional outcomes in cell replacement therapies.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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".