Ex vivo lung perfusion-to-lung transplant rat survival model with reproducible development of acute lung injury and graft rejection
Bibliographic record
Abstract
Background: Ex vivo lung perfusion (EVLP) has been clinically applied as a lung preservation and assessment tool prior to lung transplantation (LTx) and is evolving to become a platform to deliver cellular and gene therapies or inactivate pathogens. Here we aimed to investigate the utility of our recently reported rat EVLP-to-LTx model as the smallest ever experimental survival model of EVLP-to-LTx and to compare late graft endpoints between strain combinations. Methods: We tested three strains as normothermic EVLP donors: Fisher 344 (F344), Lewis (LEW), and Wistar Kyoto (WKy) rats. Then we tested three strain combinations of EVLP-to-LTx (F344-to-WKy, F344-to-LEW, and LEW-to-LEW) to compare histologic and radiologic changes. Results: F344 and LEW, but not WKy rat lungs, tolerated 4 hours of normothermic EVLP. F344-to-WKy EVLP-to-LTx developed significant histologic (as measured by acute lung injury score, ISHLT A and B grade rejection score) and radiologic (volume and mean Hounsfield units of aerated lung graft analyzed by computed tomography at day 7 after EVLP-to-LTx) changes in the lung allograft. In this strain combination, progressive deterioration with time was noted up to day 28, while F344-to-LEW grafts exhibited only mild injuries similar to LEW-to-LEW. In addition, flow cytometric analyses of F344-to-WKy EVLP-to-LTx revealed a sharp rise in activation marker expression in lung graft T cells beginning at day 3. Conclusions: Our F344-to-WKy EVLP-to-LTx model generates reproducible and clinically relevant histological, radiological, and immunological results similar to those seen in humans. The model is therefore well suited to experimental EVLP studies with long-term follow-up prior to moving to large animal and human studies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".