Restoring glucose homeostasis with stomach-derived human insulin-secreting organoids
Bibliographic record
Abstract
ABSTRACT Gut stem cells are accessible by biopsy and propagate robustly in culture, offering an invaluable resource for autologous cell therapies. Insulin-producing cells can be induced in mouse gut, but it has not been possible to generate abundant and durable insulin-secreting cells from human gut tissues to evaluate their potential as a cell therapy for diabetes. Here we describe a protocol to differentiate cultured human gastric stem cells (hGSCs) into pancreatic islet-like organoids containing gastric insulin-secreting (GINS) cells that resemble β-cells in molecular hallmarks and function. Sequential activation of the inducing factors NGN3 and PDX1-MAFA led hGSCs onto a novel differentiation path, including a SOX4 High endocrine and Galanin High GINS precursor, before adopting β-cell identity, at efficiencies close to 70%. GINS organoids acquired glucose-stimulated insulin secretion in 10 days and restored glucose homeostasis for over 100 days in diabetic mice after transplantation, providing proof of concept for a new approach to treat diabetes.
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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) | 0.000 | 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) | 0.001 | 0.001 |
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".