A Selective, Hydrogel‐Based Prodrug Delivery System Efficiently Activates a Suicide Gene to Remove Undifferentiated Human Stem Cells Within Neural Grafts
Bibliographic record
Abstract
Abstract The directed differentiation of human pluripotent stem cells (hPSCs) into defined populations has advanced regenerative medicine, especially for Parkinson's disease where clinical trials are underway. Despite this, tumorigenic risks associated with incompletely patterned and/or quiescent proliferative cells within grafts remain. Addressing this, donor stem cells carrying the suicide gene, thymidine kinase (activated by the prodrug ganciclovir, GCV), are employed to enable the programmed ablation of proliferative cells within neural grafts. However, coinciding the short half‐life of GCV with the short S‐phase of neural progenitors is a key challenge. To overcome this, a smart hydrogel delivery matrix is fabricatedto prolong GCV presentation. Following matrix embedment, GCV retains its functionality, demonstrated by ablation of hPSCs and proliferating neural progenitors in vitro. A prolonged GCV release is measured by mass spectrometry following the injection of a GCV‐functionalized hydrogel into mouse brains. Compared to suboptimal, daily systemic GCV injections, the intracerebral delivery of the functionalized hydrogel, as a “one‐off treatment”, reduce proliferative cells in both hPSC‐derived teratomas and neural grafts, without affecting the graft's functional unit (i.e., neurons). It is demonstrated that a functionalized biomaterial can enhance prodrug delivery and address safety concerns associated with the use of hPSCs for brain repair.
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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) | 0.000 | 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) | 0.000 | 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".