Reversion of passaged nucleus pulposus cells to notochordal-type cells by FoxA2 upregulation
Bibliographic record
Abstract
Notochordal cells (NC) have promise as a regenerative therapy for intervertebral disc (IVD) degeneration, but their maintenance in culture remains challenging. The study hypothesis is that nucleus pulposus (NP) cells can undergo reversion to NC-type cells through CRISPR/dCas9 activation of FoxA2. Serial passaging of cells isolated from NP shows loss of FoxA2, Brachyury (T), and Noto expression. Transient FoxA2 overexpression increased the levels of NC biomarkers, keratin, CD24, and SHH in passaged cells. So FoxA2-expressing cells were generated using CRISPR/dCas9-SAM. Analysis showed the presence of some vacuolated cells, elevated NC marker expression of Fox A2, Noto, Brachyury, and keratin and improved in vitro NP tissue formation (determined by quantifying proteoglycan content). TGFβ3 treatment enhanced tissue formation. Injected FoxA2-expressing cells survived and produced NP matrix molecules in an ex vivo bovine IVD injury model. The findings suggest FoxA2-expressing NC-type cells can be generated which may have potential to advance cell-based therapies for disc degeneration.
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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) | 0.001 | 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) | 0.001 | 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 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".