Abstract 16967: Preclinical Evaluation of Biopolymer-Delivered Endothelial Progenitor Cells in Hibernating Myocardium
Bibliographic record
Abstract
Background: Vasculogenic cell-based therapy combined with tissue engineering is a promising revascularization solution for patients with hibernating myocardium (HM), a common clinical condition. However, large animal studies are lacking and we therefore used a clinically relevant pig model of HM to examine the benefits of endothelial progenitor cells (EPCs) and biopolymer therapy in this context. We hypothesized that the delivery of EPCs within a matrix would yield greater improvements in myocardial blood flow (MBF), metabolism, and function than EPCs alone or PBS control. Methods: Twenty-three Yorkshire swine underwent placement of an ameroid constrictor on the left circumflex artery (LCx). After 2 weeks, animals underwent echocardiography, a rest and a dipyridamole-induced stress 13N-NH3 PET scan, and a rest 18FDG-PET viability scan. At the same time, EPCs were isolated and cultured for 1 week, and swine were randomized to intramyocardial injections (total: 3 ml) of PBS (n=9), EPCs (∼30 x 106; n=7), or EPCs + a collagen-based matrix (n=7). PET imaging was repeated 4 weeks post treatment, and swine were sacrificed the following week. Results: Hibernation was detected in 60% of animals and was specific to the LCx region (p=0.002). Baseline MBF was reduced at rest and stress in the affected region, compared to the remote area (1.13 ± 0.09 vs. 1.57 ± 0.15 ml/min/g at stress, respectively, p=0.01). At follow-up, MBF at stress and myocardial flow reserve (not shown) were higher in the EPC + matrix group compared to EPCs or PBS (EPCs + matrix: +21 ± 13%; EPCs -17 ± 8%; PBS: +5 ± 10%, p<0.05). This was paralleled by improved wall motion abnormalities (EPCs + matrix by 30 ± 9 %; EPCs by 22 ± 21%; PBS by 15 ± 12 %) and improved mismatch scores (EPCs + matrix by 79 ± 10%; EPCs by 55 ± 15%; PBS by 35 ± 19%)(all p<0.05). MBF at stress in the LCx segments positively correlated with smooth muscle actin staining for arterioles (r=0.7; p=0.02). Conclusions: This preclinical swine model successfully demonstrated the creation of HM, which was improved by vasculogenic cell therapy. The additional effects conferred by a collagen-based delivery matrix over EPCs alone included improved MBF in the EPC + matrix group, as well as circulatory and metabolic recovery with improvements in myocardial function.
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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 | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".