Endothelial-like Vascular Progenitor Cells (VPCs) from Allogeneic and Autologous Donors: Mobilization Features Distinct from Hematopoietic Progenitors
Bibliographic record
Abstract
Endothelial-like progenitor cells circulate in the peripheral blood (PB) and can be enumerated using cell culture-based progenitor assays. These circulating vascular progenitor cells (VPCs) are implicated in new vessel formation and regenerative potential in several animal and human models of tissue injury. Given the emerging role of VPCs in regenerative processes and the limited information on the availability of such progenitor cells, we sought to determine baseline circulating VPC levels in healthy allogeneic donors and autologous hematopoietic transplant patients. VPC numbers were also measured in peripheral blood stem cell (PBSC) grafts from both graft types. Immunohistochemistry revealed that VPC clusters obtained under our culture conditions were CD45(+) and acquired endothelial features (CD31 and vascular endothelial-cadherin) in vitro upon angiogenic stimulation and gradually lost monocytic surface markers (CD14). Before PBSC mobilization, VPCs levels varied substantially in healthy donors and were markedly lower in patients with hematologic malignancies compared with healthy allogeneic donors with 27 +/- 15 versus 99 +/- 21 VPCs/mL (mean +/- SEM), respectively (P = .001). In patients undergoing stem cell mobilization, VPCs in the PB increased from 7 +/- 2 on day 0 to 51 +/- 9 by day 7 of mobilization (P = .05), representing a median fold increase of 8.9 (range, 3.0-29.8). Although autologous transplant patients underwent more intensive mobilization, VPCs were higher in allogeneic (7.2 +/- 1.4 x 10(3)/kg) than in autologous (2.6 +/- 1.5 x 10(3)/kg) mobilized PB grafts (P = .045). To identify predictors of VPC content, graft VPCs were compared with levels of CD34(+) cells, total colony forming unit (CFU), or granulocyte-macrophage colony forming unit (GM-CFU). None of these hematopoietic progenitors correlated with VPC numbers in PBSC grafts (P = NS). However, PB monocyte levels were highly correlated with circulating VPC levels (r = 0.71, P < .0001). Thus, our analysis identified significant variability in VPCs at baseline and in PBSC grafts from healthy donors. Nevertheless, these donors remain a better source of VPCs than do autologous transplant patients. Importantly, VPC mobilization occurs independently of hematopoietic mobilization. In view of the potential role of VPCs in recovery from transplant-related tissue injury, angiogenic mobilization strategies that complement hematopoietic mobilization will need to be specifically designed.
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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".