Sustained and therapeutic delivery of factor IX in nude haemophilia B mice by encapsulated C2C12 myoblasts: concurrent tumourigenesis
Bibliographic record
Abstract
This study reports the generation of an immunodeficient murine model for haemophilia B, obtained by breeding factor IX-deficient mice with an immunodeficient mouse strain, and use of this mouse model to evaluate the long-term efficacy and safety of a gene therapy strategy for treating haemophilia B. Nude haemophilic mice were implanted with biocompatible microcapsules enclosing recombinant myoblasts secreting human factor IX. The activated partial thromboplastin time (APTT) of plasma of mice thus treated was invariably shortened 3 weeks after microcapsule implantation, and remained shortened for at least 77 days. Shortening of the APTT of the haemophilia mice coincided with the appearance of human factor IX in mice plasmas (up to 600 ng mL(-1) on day 77), and normalization of the tail-bleeding time. Thus, the microencapsulated myoblasts reversed the clinical phenotype of haemophilia B. In contrast, plasmas of immunocompetent haemophilic mice similarly implanted with microcapsules only showed a transient shortening of APTT, and coincident transient delivery of human factor IX antigen. Rapid disappearance of human factor IX from plasmas of immunocompetent mice also coincided with production of antibodies to the human transgene. Significantly, 86% of the nude haemophilia mice developed tumours of myoblast origin. Thus, while this study revealed the feasibility of this gene therapy approach to treat severe haemophilia B, it also highlights the importance of using safer cell lines to prevent tumour development.
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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 | 0.000 | 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".