Identification of growth factor conditions that reduce ex vivo cord blood progenitor expansion but do not alter human repopulating cell function in vivo.
Bibliographic record
Abstract
BACKGROUND AND OBJECTIVES: Ex vivo expansion of primitive hematopoietic cells for transplantation is an important step to realizing the optimal clinical potential of human cord blood (CB). We aimed to characterize minimal growth factor (GF) conditions that allow ex vivo expansion of primitive cells, including candidate hematopoietic stem cells. DESIGN AND METHODS: Here, we directly investigated the effect of thrombopoietin (TPO) on progenitors and repopulating cells using serum-free culture of CB Lin-CD34+CD38- cells in two different minimal GF conditions: stem cell factor (SCF)+FLT-3-L (termed S/F) and SCF+FLT-3-L+TPO (termed S/F/T). RESULTS: While S/F media supported only low levels of total cell and CFU (colony-forming unit) expansion, the addition of TPO (S/F/T) partially restored cell proliferation, and completely restored CFU expansion to levels observed using full GF conditions (SCF+FLT-3-L+interleukin (IL)-3 (IL-3)+ IL-6+ granulocyte colony-stimulating factor (G-CSF). Intravenous transplantation of either S/F- or S/F/T-expanded cells into NOD/SCID mice resulted in similar frequencies and levels of multilineage reconstitution. INTERPRETATION AND CONCLUSIONS: The use of minimal cytokine stimulation and simultaneous assessment of CFU and SRC indicate that hematopoietic progenitors and in vivo-detected repopulating cells are differentially responsive to TPO; CFU expand in response to TPO but SRC do not. In addition, our study suggests that TPO can functionally replace IL-3+IL-6+G-CSF for CFU expansion of ex vivo cultured CB Lin-CD34+CD38- hematopoietic stem cells.
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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".