Expansion of umbilical cord blood derived oligodendrocytes
Bibliographic record
Abstract
Transplantation of children with lysosomal storage diseases (LSD) with unrelated donor-umbilical cord blood (UCB) is effective in preventing onset and progression of severe neurologic symptoms if performed early in the course of the disease. Unfortunately, many children are not diagnosed before moderate to severe neurologic damage has occurred. These symptomatic children experience disease stabilization after transplant but do not regain lost function. This may be due to the fact that irreversible damage has occurred or, conversely, that stem cells transit to the brain too slowly to effect neural cell repair. To address this problem, we have developed in vitro methods to isolate and characterize oligodendrocytes derived from human UCB. We previously described these methods and the initial characterization of these cells (Hall et al). Continuing to advance this work, we now are focusing on further characterization and expansion of this population of cells in preparation for a phase I human clinical trial in patients with symptomatic LSD. Human UCB is red cell depleted with hetastarch, mononuclear cells are isolated with ficol density separation, and plated at a density of 5 × 105 cells/ml in media containing neurotropin 3, vascular endothelial growth factor, and platelet derived growth factor. The adherent cells are washed 2× per week for 2 weeks, then passaged and replated at a density of 5 × 103 cells/ml with media changes twice weekly, once with the original oligodendrocyte media and the second with NeuroCult media (StemCell Technologies, Vancouver). Cells expand with an approximate doubling time of 6.5 days. After 4 and 6 week periods, a 16- and 64-fold expansion can be seen, respectively. We anticipate that using a 20% fraction (200 × 106 cells) of a cord blood unit we can obtain 33 × 108 cells in 6 weeks. Oligodendrocyte lineage identity of these cells, post expansion, was confirmed by PCR based methods with expression of myelin basic protein, nestin, PLP, and Neurogenin 3. We conclude that oligodendrocytes can be isolated and expanded from human UCB yielding sufficient numbers of cells for testing in phase I human trials to facilitate neural cell repair in patients with advanced LSD.
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 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".