Islet transplantation in the discordant tilapia-to-mouse model: a novel application of alginate microencapsulation in the study of xenograft rejection
Bibliographic record
Abstract
BACKGROUND: Tilapia islet xenograft rejection is characterized by infiltration with macrophages (Mphis), eosinophils (Ephis), and T lymphocytes. The presence of these cells indicates they contribute to rejection; therefore, an attempt was made to assess their role through host immunomodulation. METHODS: Tilapia islet cells were transplanted under the kidney capsule of streptozotocin diabetic Balb/c mice, which were then treated with one of several immunomodulatory regimes targeting Mphis, Ephis, or T cells. Mphis were depleted using either silica or liposome-entrapped Cl2MDP. Ephi migration was blocked using monoclonal antibodies (mAbs) targeting interleukin (IL)-4 or IL-5. T-cell function was altered with mAbs targeting CD3, CD4, or CD8. Finally, T helper (Th)1 and Th2 activity was altered by depleting essential Th1 or Th2 cytokines with mAbs or by promoting a Th1 response with the injection of exogenous IL-12. The effects of antibody-mediated immunomodulation on graft survival were initially screened by cotransplanting alginate-encapsulated, mAb-secreting hybridoma cells into the peritoneal cavity at the time of islet transplantation. Significant prolongation was then confirmed using purified antibodies injected at the time of islet transplantation. Rejected grafts were examined histologically, and immunohistochemistry was used to assess the cellular infiltrates for each of the treatment groups. RESULTS: Modulation of Mphis and Ephis alone did not significantly delay functional rejection of tilapia islet grafts (maximal mean graft survival time [mGST]=7.1+/-1.7 and 9.4+/-3.4, respectively) compared with untreated controls (mGST=8.2+/-1.0). Treatment of transplanted animals with antibodies against CD3 or CD4 significantly promoted graft survival (maximal mGST=16.3+/-5.8 and 34.0+/-11.6, respectively), whereas targeting CD8 and Th1 and Th2 cytokines showed no prolonging effect (maximal mGST=7.8+/-2.9 and 9.5+/-4.3, respectively). CONCLUSION: Our results indicate that rejection in the tilapia-to-mouse model follows a pattern similar to other models of discordant islet cell xenotransplantation.
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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 | 0.001 |
| 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".