Liposomal encapsulation significantly enchances the immunosuppressive effect of tacrolimus in a discordant islet xenotransplant model1
Bibliographic record
Abstract
BACKGROUND: Encapsulation of tacrolimus (TAC) in a lipid bilayer to form liposome-encapsulated tacrolimus (LTAC) alters the biodistribution profile, half-life, and efficacy in organ allotransplantation models. LTAC has not been applied to either cell transplantation or xenotransplantation. METHODS: To test the efficacy of LTAC in a discordant islet xenograft model, tilapia (fish) islets were transplanted under the left kidney capsules of streptozotocin-diabetic Balb/c mice. Recipient mice (groups I-VI) were treated with: I, untreated; II, empty liposomes; III, TAC (2 mg/kg/day); IV, TAC (5 mg/kg/day); V, LTAC (2 mg/kg/day); or VI, LTAC (5 mg/kg/day); all treatments were for 35 days or until rejection (i.e., two glucose measurements >200 mg/dl). Graft-bearing kidneys were removed for histology after rejection. RESULTS: Mean graft survival time (mGST) for control groups I and II were 6.7+/-1.4 (n=6) and 7.5+/-1.3 days (n=4), respectively. Daily TAC treatment at 2 mg/kg/d (III) did not prolong graft function (mGST=7.7+/-1.6; n=6) although 5 mg/kg/day (IV) produced minimal prolongation to 12.8+/-4.8 days (n=12). Treatment with LTAC at 2 mg/kg/day (V) significantly prolonged mGST to 26.6+/-4.9 (n=5); however, all recipients rejected during treatment (i.e.,<35 days). LTAC at 5 mg/kg/day (VI) further prolonged mGST to 39.9+/-11.8 days (n=12) with only one mouse rejecting before day 35. Histologically, at the time of functional rejection, grafts were generally either totally or partially effaced by mononuclear cells, eosinophils, and fibrosis. In groups VI, islet grafts removed from two mice that died while they were normoglycemic and from a mouse terminated while it was normoglycemic at day 36 were viable, well-granulated, and free from cellular infiltration. The group VI grafts examined at rejection (i.e., 1-2 weeks after discontinuing LTAC) were generally totally obliterated and were in two instances associated with nodular aggregates of atypical lymphocytes resembling posttransplant lymphoproliferative disorder. CONCLUSIONS: LTAC is the most potent immunosuppressive compound we have tested in our discordant fish-to-mouse islet xenograft model; however, toxicity is an issue at high doses.
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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) | 0.001 | 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".