Abstract 1283: Endothelial Nitric Oxide Synthase Promotes Mesenchymal Stem Cell Migration Towards the Ischemic Myocardium
Bibliographic record
Abstract
Background: Bone marrow mesenchymal stem cells (MSCs) migrate from bone marrow towards the heart and contribute to cardiac repair post myocardial infarction. However, mechanisms by which MSCs migrate to the ischemic heart remain unclear. The present study investigated the role of endothelial nitric oxide synthase (eNOS) on MSC migration towards the ischemic myocardium and whether stromal cell derived factor-1 (SDF-1) contributes to the eNOS-mediated MSC migration. Methods and Results: MSCs were isolated from wild-type (WT) bone marrow and cultured in vitro for 3 generations. Coronary microvascular endothelial cells were isolated from adult mouse hearts and seeded on inserts for transendothelial migration assay. Neonatal cardiomyocytes were isolated from WT, eNOS −/− and eNOS transgenic (Tg) mice, cultured to subconfluence and subjected to 30 min of anoxia followed by 6 hours of reoxygenation (A/R). The conditioned medium was collected and served as a chemoattractant. MSC migration was significantly decreased in eNOS −/− compared to WT conditioned medium (9.8± 1.8% vs. 14.7±2.3%), but increased in eNOS-Tg conditioned medium (38.0±4.5%, P <0.05). SDF-1 protein secretion was significantly decreased in eNOS −/− but increased in eNOS-Tg conditioned medium. To examine MSC migration in vivo, WT, eNOS −/− or eNOS-Tg mice were subjected to myocardial ischemia for 45 min followed by 24 hrs of reperfusion (I/R). Immediately after reperfusion, GFP + MSCs were administered via a tail vein. GFP + cells in the ischemic region were significantly decreased in eNOS −/− compared to WT hearts (3.4±0.3 vs. 5.6±0.4 cell per mm 2 , P<0.05) but significantly increased in eNOS-Tg compared to WT (10.2±1.6 vs. 5.6±0.4 cell per mm 2 , P<0.05). Furthermore, SDF-1 mRNA and protein expression was increased in eNOS-Tg as compared to WT and eNOS −/− after myocardial I/R. Conclusions: eNOS promotes MSC migration towards the ischemic myocardium. This is likely due to an upregulation of SDF-1.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".