Innate immune modulation as a mechanism for therapeutic action of early EPCs in a nude rat model of pulmonary hypertension
Bibliographic record
Abstract
Early and late‐outgrowth endothelial progenitor cells (EPCs) were cultured from human leukapheresis samples and tested for therapeutic efficacy in a nude rat, monocrotaline (MCT)‐induced model of pulmonary hypertension (PH). Three days after injection of MCT, 10 6 cells were administered to nude rats via central venous injection. Three weeks after cell injection, right ventricular systolic pressure was elevated in MCT treated animals (61 ± 3.8 vs. 27 ± 0.5 mmHg no MCT control). The administration of early‐EPCs prevented the onset of PH (33 ± 3.2 mmHg), while delivery of late‐EPCs produced no improvement (60 ± 4.0 mmHg). Analysis of cell retention by histology and PCR revealed that, despite the therapeutic benefit of early‐EPCs, neither cell type was retained within the lung at 24 hours post injection. A subsequent in vitro characterization of early‐EPCs revealed a capacity to modulate the innate immune response in a manner similar to that of dendritic cells. Early‐EPCs, which are positive for CD14, MHC II, CD86 and CD11c, and negative for CD1a and CD83, increased surface expression of CD86 and CD83 and decreased surface CD14 in response to stimulation with LPS. Exposure to LPS also induced the secretion of IL‐10 but not IL‐12. As with dendritic cells, co‐culture of early‐EPCs with autologous natural killer (NK) cells in the presence of LPS induced NK cytotoxicity, suggesting a potential mechanism of therapeutic action.
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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) | 0.001 | 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".