10-7: CLOSED CULTURE SYSTEMS FOR STEM CELL-DERIVED ISLET BIOMANUFACTURING
Bibliographic record
Abstract
Introduction: Islet transplantation, including stem cell-derived islets (SC-islets), show promise as long-term treatment for type 1 diabetes. Published protocols for SC-islet biomanufacturing typically follow 7 stages of directed differentiation, either using adherent culture at initial stages before transitioning into suspension, or with all steps performed in suspension. Preclinical research applies protocols with several manual handling steps, typically applying functionally open culture systems such as well plates or T-flasks. Many protocols also apply controlled aggregation systems to generate SC-islets in the transition to suspension. Clinical translation will require transfer to vessels and approaches amenable to current good manufacturing practices (cGMP). We describe a series of closed culture vessels made from fluorinated ethylene propylene (FEP), a material that is chemically inert with low leachables and high oxygen permeability[1,2]. Methods: FEP culture vessels were applied systematically at different stages of the SC-islet biomanufacturing process. We investigated pluripotent stem cell culture in adherent cultures on FEP, differentiation in adherent cultures up to pancreatic endoderm (Stage 4 cells), controlled aggregation in FEP microwells, and finally suspension culture of SC-islets. Results: No significant differences between FEP vessels and tissue culture polystyrene controls were observed at Stage 1 (definitive endoderm, >95% SOX17+). Optimization of handling procedures allowed successful production of Stage 4 cells (>50% PDX1+NKX6.1+) in FEP vessels. As compared to a commercial controlled aggregation system, FEP microwells offered a simplified workflow without the need for centrifugation steps nor addition of anti-adhesion solutions, while achieving uniform aggregate sizes and high viability. Finite element models of oxygen transport (COMSOL Multiphysics) show an advantage of FEP over the commercial system in terms of oxygen supply to the aggregated cells. Finally, optimization of mixing conditions and vessel geometries led to promise in maintaining SC-islets in suspension. Conclusions: Closed culture vessels made from FEP may offer a versatile end-to-end platform for SC-islet biomanufacturing under cGMP.
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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 | 0.001 | 0.001 |
| 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 | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".