Abstract 5804: Embryonic Stem Cell-Derived Endothelial Cells Engraft Into the Ischemic Hindlimb and Restore Perfusion
Bibliographic record
Abstract
Peripheral arterial disease (PAD), which affects about 10 million Americans, is typically due to atherosclerotic arterial occlusive disease of the limbs and is associated with dysfunctional vascular endothelium. Cell-based therapy using endothelial cells derived from embryonic stem cells (ESC-ECs) is a promising approach for regenerating the endothelium. However, studies that characterize the localization and engraftment of embryonic stem cells (ESCs) and ESC-ECs into the ischemic limb are limited. In this study, we examined the survival, localization, and functional effects of exogenously administered ESC-ECs for repair of hindlimb ischemia, which is a murine model of PAD. Murine ESCs or ESC-ECs were stably transduced with a construct for bioluminescence imaging (BLI) and fluorescent detection. In a syngenic murine model of hindlimb ischemia, ESCs or ESC-ECs were delivered by intramuscular (IM), intra-femoral artery (IA), or intra-femoral vein (IV) injections (n=5 in each group). For 2 weeks, cell survival and localization were tracked by BLI and confirmed by gene expression, and functional improvement was assessed by laser Doppler blood perfusion. BLI results showed ESC persisting in the ischemic limb after IM or IA, but not after IV administration. Regardless of the route of administration, ESCs were detected outside of the hindlimb circulation in the spleen or lungs. ESCs did not improve limb perfusion, and induced teratomas. In contrast, ESC-ECs localized to the ischemic limb in all cases as assessed by BLI. Immunohistochemical studies confirmed the engraftment of ESC-ECs into the limb vasculature after 2 weeks. Intriguingly, ESC-ECs were not detected in the spleen or lungs after 2 weeks, even after IV administration. Furthermore, ESC-ECs improved limb perfusion. In comparison to parental ESCs, ESC-ECs preferentially localized in the ischemic hindlimb, even after IV delivery. ESC-EC localization was temporally related to the improvement in hindlimb perfusion, which was associated with engraftment of ESC-ECs into the ischemic microvasculature. This research has received full or partial funding support from the American Heart Association, Western States Affiliate (California, Nevada & Utah).
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.006 | 0.002 |
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".