P4–370: Long–term survival of human CNS stem cells and their progeny in immunodeficient, plaque–producing APP transgenic mice
Bibliographic record
Abstract
To be an effective therapy for Alzheimer's disease (AD), human central nervous system stem cells (hCNS–SC) must be able to engraft, proliferate and differentiate in an environment with high levels of Aβ peptide and amyloid plaques. Three transgenic mouse lines, Tg(APPNL)2576, Tg(APPNLI)19959 and Tg(APPNLI)CRND8, that differ in the levels of Aβ peptides and age at onset of amyloid plaque deposition were used to model this condition. The goal of this study was to evaluate the effects of Aβ and plaques on survival of hCNS–SC and their progeny. Plaques appear in Tg2576 mice by 10 months and in Tg19959 or TgCRND8 by 3 months. Immunodeficient transgenic lines incapable of rejecting transplanted human cells were produced by backcrossing to mice homozygous for the severe combined immunodeficiency (scid) allele of the Prkdc gene. Highly purified and well–characterized banked hCNS–SC lines were used for transplantation by stereotaxic injection into the lateral ventricles of neonatal or 1 day–old litters of scid/scid transgene–positive and transgene–negative mice. Engraftment was assessed 6 weeks after injection using monoclonal antibodies specific for human cytoplasmic antigens or nuclei; no effect of high level Aβ expression on human cell survival was seen in any of the Tg lines. Mice were aged and sampled periodically for engraftment. Human cells were easily identified in Tg(APP) and non–transgenic mice months after injection. To assess the feasibility of hCNS–SC therapy for AD patients, cells were injected stereotaxically into the hippocampi of adult scid/scid Tg(APP)19959 mice with established plaques. No effect on survival of the human cells was noted and many cells were found in close proximity to plaques. The finding that high Aβ levels or amyloid plaques did not compromise survival of the transplanted cells suggests the hCNS–SC transplantation in AD may be a viable neuronal replacement therapy. Prolonged survival of hCNS–SC in an AD–like environment suggests that transplanted stem cells might provide a new source of neuronal cells and also offers the option to use genetically modified cells as a vehicle for delivery of therapeutic proteins.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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".