Human Cord Blood Cells with Rapid In Vivo Platelet Regenerating Activity in NOD/SCID-IL-2Rγc-/- Mice Show Variable Aldehyde Dehydrogenase Activity.
Bibliographic record
Abstract
Abstract Abstract 2429 Poster Board II-406 Human cord blood (CB) has emerged as an attractive source of hematopoietic cells for patients lacking a suitable donor. However, marked delays in platelet and immune recovery pose significant challenges to the use of CB cells as transplants for either children or adult patients. These difficulties in the use of CB have been attributed to low absolute numbers of repopulating cells (RCs) in most CB units which is not readily overcome by simply combining multiple units. Xenotransplantation of human hematopoietic cells into highly immunodeficient sublethally irradiated NOD/SCID mice has proven to be a powerful approach to characterize different types of primitive human hematopoietic cells with repopulating potential. However, the residual NK activity intrinsic to NOD/SCID mice poses a significant barrier to the engraftment of intermediate types of repopulating human cells and also to the terminal stages of their differentiation, as shown by recent studies using more immunodeficient mice as hosts. Nevertheless, the cells responsible for early platelet recovery post-transplant and factors that regulate their activity remain largely unknown. To address this issue, we have developed a quantitative and sensitive assay for characterizing the phenotypes of human CB cells that regenerate mature platelets detectable in the blood of NOD/SCID-IL-2Rγc-/- mice 3-6 weeks post-transplant. Lineage marker-negative (Lin-) human CB cells were stained with Aldefluor and then those with low light side-scattering properties were further separated by FACS according to whether they displayed aldehyde dehydrogenase activity above (ALDH+) or below (ALDH-) that detected in the presence of an ALDH inhibitor. Assays of different pooled human CB preparations showed that the most primitive class of in vitro megakaryocyte (Mk) colony-forming cells and cells responsible for rapid human platelet production in NOD/SCID-IL-2Rγc-/- mice were variably and comparably distributed between the small ALDH+ and prevalent ALDH- fractions. From 3 experiments, the following values were obtained for the ALDH+ and ALDH- subsets, respectively; ALDH+ - mature CFU-Mk = 47.8±21.3% of the total Lin- fraction, intermediate CFU-Mk = 66.3±25.4%, primitive CFU-Mk = 75.5±14.0%, 3-week platelet-producing STRC = 63.8±12.3%, 6-week platelet-producing STRC = 81.5±5.8%; and ALDH- - mature CFU-Mk = 52.2±21.3% of the total Lin- fraction, intermediate CFU-Mk = 33.7±25.4%, primitive CFU-Mk = 24.5±14.0%, 3-week platelet-producing STRC = 36.2±12.3%, 6-week platelet-producing STRC = 18.5±5.8%. Limiting dilution assays revealed 1 in 830 Lin-ALDH+ CB cells to be a cell that can produce detectable platelets in vivo within 3 weeks (95% CI = 1 in 534 to 1 in 1290) but only 1 in 1996 (95% CI = 1 in 1226 to 1 in 3247) within 6 weeks. The present study demonstrates the feasibility of using NOD/SCID-IL-2Rγc-/- mice for the sensitive detection of human CB cells with in vivo platelet regenerating activity and suggests that these may be closely related to primitive cells with in vitro Mk clonogenic activity (>50 Mk per colony). Biologically important platelet progenitors may thus be heterogeneous with respect to ALDH+ activity. Disclosures: No relevant conflicts of interest to declare.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".