Abstract 2897: Targeting Engraftment of Endothelial Progenitor Cells to Ischemic Tissue by Ultrasound-mediated Transfection of Stromal Cell Derived Factor-1
Bibliographic record
Abstract
The homing of endothelial progenitor cells (EPC) to sites of ischemic injury is critical to successful neovascularization. We hypothesize that ultrasound-mediated (UM) transfection of stromal-cell derived factor-1 (SDF-1) would enhance engraftment of exogenously administered EPCs and improve neovascularization in a rat model of chronic hindlimb ischemia. Methods: Bone-marrow derived EPCs were isolated from donor F344 rats, cultured for 7 days, labelled with CMTMR and injected (1 x 10 6 ) into recipient animals via a jugular vein. Unilateral hindlimb ischemia was created by iliac artery ligation in 32 rats. At day 14 post ligation, microvascular blood volume (MBV) and blood flow (MBF) in the hindlimb muscles were assessed by contrast-enhanced ultrasound (CEU). Rats were assigned to 4 treatment groups: control untreated animals, EPCs alone, UM delivery of SDF-1 plasmid (500 μg DNA + 1x10 9 cationic microbubbles), and both UM delivery of SDF-1 + EPCs (n=8 per group). Perfusion was re-assessed at day 28. EPC engraftment was assessed using fluorescent microscopy. Circulating exogenous EPC numbers were determined by FACS at various time-points post injection. Results: Prior to EPC delivery, normalized MBV and MBF in ischemic muscle were similarly reduced in all groups. Control animals showed no changes in perfusion over time. By day 28, EPC treated animals had a significant increase in normalized MBV (1.04±0.24 vs 0.67±0.22, p<0.001), without significant improvements in MBF (0.44±0.13 vs 0.33±0.15, p=NS), while SDF-1/EPC treated animals had significant improvement in both normalized MBV (1.33±0.51 vs 0.67±0.22, p<0.001), and MBF (0.55±0.26 vs 0.33±0.15, p<0.001). Maximal exogenous circulating EPCs could be detected at 72 hours post injection. Fluorescent microscopy showed little to no CMTMR labelled cells in the non-ischemic hindlimb in all groups. In comparison, a rich population of cells was found in the ischemic hindlimb of both the SDF-1/EPC and EPC treated animals, with the SDF-1/EPC animals demonstrating the greatest density of EPCs. Conclusions: Ultrasound-mediated transfection of SDF-1 improves intravenous EPC targeting, enhancing EPC engraftment into chronically ischemic tissue and leading to greater neovascularization response.
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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 | 0.000 |
| 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".