Enabling airway regenerative medicine with enhanced primary basal cell culture
Bibliographic record
Abstract
Primary epithelial cells can be cultured in vitro on mitotically-inactivated 3T3-J2 fibroblasts in cell culture medium supplemented with growth factors. Cells expanded using this method were used to regenerate the epidermis of a child with severe junctional epidermolysis bullosa (Hirsch, T. et al. Nature 2017). However, airway cells grown in these conditions have limited proliferation rate, longevity before senescence, and capacity for clonal culture. We have previously shown that the addition of the small molecule Y-27632 to epithelial culture medium improved the proliferation and culture duration of primary airway basal cells (Butler, C. et al. AJRCCM 2016). Here, we report that the addition of commercially available small molecule ‘compound E’, to be disclosed at the meeting, to basal cell growth medium enhanced the clonogenicity, proliferation rate, longevity, and strength of cell attachment. Basal cells retained their self-renewal capacity and ability to differentiate in air-liquid interface and organoid cultures. Genome integrity was preserved after extensive culture. Mechanistically, ‘compound E’ activated AKT signalling to promote basal cell survival. Basal cells were expanded to the estimated number required to repopulate an adult tracheal graft in an average of 14.6 days (n=9; range 12-18 days). Supporting their use in regenerative medicine, orthotopically transplanted cells reconstituted the epithelium in immunocompromised mice. Overall, we demonstrate significant improvement in the quality of primary airway basal cell cultures. Cells expanded in ‘compound E’ have applications in airway cell and gene therapy, bioengineering, and disease modelling.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 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 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".