Cholangiocytes derived from induced pluripotent stem cells for disease modeling
Bibliographic record
Abstract
PURPOSE OF REVIEW: Biliary diseases are a significant cause of morbidity and mortality. Challenges in establishing accurate in-vitro methods to model human bile duct diseases and evaluate therapies have contributed to a lack of effective medical treatments. The recent discovery of strategies to reprogram human somatic cells to a state of induced pluripotency has opened up new possibilities for studying both development and disease in a wide variety of human tissues. This review was undertaken to summarize the recent progress made in generating biliary tissue from induced pluripotent stem cells (iPSCs) and the application of this technology to biliary disease modeling. RECENT FINDINGS: Several groups have reported defined differentiation protocols that incorporate key signaling cues from normal biliary development to yield cholangiocyte-like cells from wild-type human iPSCs that demonstrate epithelial morphology in two and three-dimensional culture, cholangiocyte markers, biliary gene expression profiles, and functional attributes consistent with biliary epithelium. Key features of Alagille syndrome and polycystic liver disease can be modeled with iPSC-derived cholangiocytes, whereas the use of iPSCs from cystic fibrosis patients has facilitated not only modeling of cystic fibrosis biliary disease but also in-vitro correction of the disorder with pharmacological agents. SUMMARY: Mature, functional cholangiocytes can be derived from human iPSCs and utilized to model biliary diseases in vitro. These advances should facilitate further research to improve our understanding of the pathophysiology of cholangiopathies and evaluate novel treatments. In the future, this technology will likely form a key element of tissue replacement strategies.
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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) | 0.002 | 0.001 |
| 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 | 0.001 |
| 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".