366 Humanized Skin Model in Severe Combined Immune Deficient Pigs
Bibliographic record
Abstract
Hypertrophic scarring after burns is common resulting in significant disfigurement and dysfunction. Further advances in understanding the pathobiology of scarring and the development of novel therapies aimed at reducing scarring are hindered by the lack of appropriate large animal models. Transplantation of human xenografts onto immune compromised mice is a powerful research tool for studying wound healing. However, differences in healing between humans and mice and their small size limits this model. Recently, a severe combined immune deficiency (SCID) pig was accidentally discovered. We determined whether human cadaver skin xenografts transplanted onto SCID pigs would survive and not be rejected. Split thickness, meshed (1:1.5), cryopreserved human cadaver skin obtained from a skin bank was transplanted onto 10 partial thickness dermatome wounds in each of two normal domestic pigs and two SCID pigs. Autografts (n=2/animal) from the 4 animals were used as controls. Animals were followed for 4 weeks and periodic digital images and full thickness biopsies were obtained to monitor healing using H&E stains as well as T-cell specific CD3-antibodies. Human specific HLA antibodies were used to determine the origin of the transplanted skin in SCID pigs. In normal pigs, all autografts were engrafted and healed with minimal if any inflammation and scarring. All human xenografts were rejected by the normal pigs within 5-11 days and associated with an intense T-cell inflammatory response. In contrast, both autografts and xenografts were engrafted and survived the 28-day study in the SCID pigs with minimal inflammation in only 1/20 xenografts and no gross scarring in any wounds. Human specific antibodies (HLA-ABC) confirmed the human source of the healed xenografts. This study serves as proof-of-concept that human cadaver skin survives on SCID pigs for at least 28 days. Further development of this model is ongoing to determine if human hypertrophic scars or keloids can be transplanted onto SCID pigs. We believe that a humanized scar model in pigs will be helpful in the development of novel therapies aimed at preventing or reducing hypertrophic scarring after burns.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 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".