Abstract 226: Recellularization of Xenograft Heart Valves Reduces the Xenoreactive Immune Response in an <i>In Vivo</i> Rat Model
Bibliographic record
Abstract
Background: Current xenograft valve constructs provoke an intense immune response that may lead to valve dysfunction. Our aim was to address the role of autologous mesenchymal stem cell (MSC) recellularization of xenogenic valves on the activation of the xenoreactive immune response in an in-vivo rat model. Methods: Explanted aortic valve constructs from female Hartley guinea pigs were procured and decellularized, followed by recellularization with syngeneic Sprague-Dawley rat MSCs. The recellularized aortic valve xenografts were then implanted into the infrarenal aorta of recipient female Sprague-Dawley rats. Grafts were implanted as either syngeneic grafts, non-decellularized (fresh), decellularized and recellularized xenografts. Rats were euthanized after 7-days, exsanguinated and the grafts explanted. Total serum immunoglobulin was quantified and histological analysis perfomed to analyze the immune response. Results: Overall survival to endpoint was significantly lower in the decellularized xenograft group (67%; 4/6), compared to fresh (100%; 6/6) and recellularized grafts (100%; 6/6). Similarly grafts in the decellularized group were more likely to have completely thrombosed (50%; 2/4), compared to fresh (33%; 2/6) and recellularized grafts (0%; 0/6). Decellularized guinea pig xenografts, when implanted into rats in-vivo , result in significantly reduced total serum immunoglobulin production and significantly reduced graft cellular infiltrate when compared to fresh xenografts. Moreover, when decellularized guinea pig xenografts were recellularized with syngeneic rat MSCs there was an additional decrease in total serum immunoglobulin production and graft cellular infiltrate when compared to both fresh and decellularized xenografts. Importantly, recellularized guinea pig xenografts had an equivalent total immunoglobulin production and graft cellular infiltrate when compared to syngeneic rat aortic valve controls. Conclusions: Autologous MSC recellularization of xenogenic valves reduces the xenoreactive immune response in an in-vivo rat model and may be an effective approach to decrease the progression of xenograft valve dysfunction.
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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 | 0.000 | 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".