Short-Term Exposure of Umbilical Cord Blood CD34+ Cells to Human Platelet Lysate and Cytokines Enhances Engraftment
Bibliographic record
Abstract
Umbilical cord blood (UCB) is a widely used source of stem cells in therapies of malignant and nonmalignant hematologic diseases and metabolic disorders. However, UCB grafts are limited by low number of stem cells, which is associated with delayed hematopoietic and immunologic recovery. Intra-bone marrow (IBM) injection has been proposed as a strategy to bypass homing inefficiencies associated with intravenous hematopoietic stem cell (HSC) transplantation, thus increasing the number of HSCs that engraft. Despite physical delivery into the bone marrow cavity, many donor cells are rapidly redistributed by vascular perfusion, thus potentially compromising the efficacy of this approach. The objective of this study was to evaluate the ability of human platelet lysate (hPL) to improve HSC anchorage into the bone marrow and, consequently, to improve engraftment. HSC were isolated using the EasySep Human CD34-Positive Selection Kit (STEMCELL Technologies Inc., Vancouver, BC, Canada), and purity was assessed by flow cytometry. HSCs were then seeded in the wells of a 24-well microplate and exposed to increasing concentrations of hPL with or without cytokines for 24 hours at 37°C, 5% CO2. At the end of the culture, HSC chemotaxis toward rhSDF-1 was determined in vitro using a Transwell (Thermo Fisher Scientific, Burlington, ON, Canada), and engraftment in NSG mice was also evaluated. Short-term exposure of cord blood CD34+ cells to a combination of human platelet lysate (hPL) and cytokines resulted in a significant increase (up to threefold) in the expression of the CD34 antigen on HSCs. This effect was closely correlated to a significantly increased (up to sevenfold) migration toward an rhSDF-1 concentration gradient. In addition, IBM injection of CD34+ cells previously exposed to hPL + cytokines into NSG mice showed significantly increased engraftment as measured by human platelet numbers (704.9 ± 230.3 vs. 3,193.0 ± 1,806.7 human platelets [hplt]/μL of blood; p = .005), human CD45 (13.2% ± 4.4% vs. 22.2% ± 1.4%; p = .02) and human CD34+ cells (2.4% ± 1.2% vs. 6.6% ± 1.1%; p = .006) for untreated and treated cells, respectively. The use of hPL + cytokines as a short-term conditioning treatment for UCB could be an attractive strategy to improve clinical outcomes following IBM injection.
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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 | 0.000 |
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 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".